Original Article
Angiotensin II Blockade and Aortic-Root Dilation in Marfan's Syndrome
N Engl J Med 2008; 358:2787-2795June 26, 2008
- Abstract
Background
Progressive enlargement of the aortic root, leading to dissection, is the main cause of premature death in patients with Marfan's syndrome. Recent data from mouse models of Marfan's syndrome suggest that aortic-root enlargement is caused by excessive signaling by transforming growth factor β (TGF-β) that can be mitigated by treatment with TGF-β antagonists, including angiotensin II–receptor blockers (ARBs). We evaluated the clinical response to ARBs in pediatric patients with Marfan's syndrome who had severe aortic-root enlargement.
Methods
We identified 18 pediatric patients with Marfan's syndrome who had been followed during 12 to 47 months of therapy with ARBs after other medical therapy had failed to prevent progressive aortic-root enlargement. The ARB was losartan in 17 patients and irbesartan in 1 patient. We evaluated the efficacy of ARB therapy by comparing the rates of change in aortic-root diameter before and after the initiation of treatment with ARBs.
Results
The mean (±SD) rate of change in aortic-root diameter decreased significantly from 3.54±2.87 mm per year during previous medical therapy to 0.46±0.62 mm per year during ARB therapy (P<0.001). The deviation of aortic-root enlargement from normal, as expressed by the rate of change in z scores, was reduced by a mean difference of 1.47 z scores per year (95% confidence interval, 0.70 to 2.24; P<0.001) after the initiation of ARB therapy. The sinotubular junction, which is prone to dilation in Marfan's syndrome as well, also showed a reduced rate of change in diameter during ARB therapy (P<0.05), whereas the distal ascending aorta, which does not normally become dilated in Marfan's syndrome, was not affected by ARB therapy.
Conclusions
In a small cohort study, the use of ARB therapy in patients with Marfan's syndrome significantly slowed the rate of progressive aortic-root dilation. These findings require confirmation in a randomized trial.
Media in This Article
Figure 1
Mean Annual Rate of Change in Absolute and Normalized Aortic Diameters before and after Initiation of Therapy with an Angiotensin II–Receptor Blocker (ARB).Figure 2
Change in Aortic-Root Diameter Standardized According to the Time of Initiation of Therapy with an Angiotensin II–Receptor Blocker (ARB).Article Activity
- Article
Marfan's syndrome, an autosomal dominant connective-tissue disorder affecting approximately 1 in 5000 people, is caused by mutations in the gene encoding fibrillin-1 (FBN1).1,2 FBN1 mutations lead to defects in multiple organ systems, of which the most life-threatening is progressive enlargement and dissection of the aortic root.3,4 Current medical management of Marfan's syndrome is focused on serial cardiac-imaging studies and the use of pharmacologic agents to reduce hemodynamic stress on the aortic wall. Pharmacologic treatment often involves the use of beta-adrenergic–receptor antagonists (beta-blockers), although other agents, such as angiotensin-converting–enzyme (ACE) inhibitors and calcium-channel blockers, have been used in patients who have unacceptable adverse events or no response to beta-blockers.5-7
Studies in a mouse model of Marfan's syndrome have shown that a deficiency of fibrillin-1 in the extracellular matrix leads to excessive signaling by transforming growth factor β (TGF-β), an event that probably contributes to the pathogenesis of multiple phenotypic features of Marfan's syndrome, including progressive enlargement of the aortic root.8-11 These genetically engineered mice, in which the pathologic changes in the aortic root closely mimic those seen in humans, were subsequently used to demonstrate the therapeutic benefit of treatment with TGF-β antagonists in vivo. The development of pathologic changes in the aortic wall and the progressive dilation of the aortic root were attenuated or prevented by systemic treatment with a TGF-β–neutralizing antibody or the angiotensin II–receptor blocker (ARB) losartan, an antihypertensive medication known to inhibit TGF-β signaling.10,12 In comparison, mutant mice treated with the beta-blocker propranolol continued to show substantial aortic-wall pathologic changes and had only a moderate reduction in the rate of aortic-root dilation. These findings led us to hypothesize that treatment with ARBs might be effective for the prevention of aortic-root enlargement and associated cardiovascular pathologic changes in patients with Marfan's syndrome.
Methods
Study Design and Patients
We retrospectively reviewed the records of all pediatric patients treated in the medical genetics clinic of Johns Hopkins Hospital who met the Ghent diagnostic criteria13 for Marfan's syndrome and who were followed prospectively from October 1996 through November 2007. The diagnosis of Marfan's syndrome was confirmed in each patient after exclusion of other known congenital aneurysm syndromes on the basis of distinguishing phenotypic features, molecular mutation analysis, or both (see the Supplementary Appendix, available with the full text of this article at www.nejm.org). This retrospective study was approved by the institutional review board of Johns Hopkins University, which waived the requirement for informed consent.
We identified a cohort of 18 patients with Marfan's syndrome, 14 months to 16 years of age, who had begun ARB therapy between November 2003 and May 2006 and had continued to receive the therapy for at least 1 year of follow-up. An additional patient was identified who was prescribed an ARB, but this patient was excluded from the analysis after we found documented periods of nonadherence to therapy. The decision to initiate ARB therapy in these patients was made on clinical grounds during routine visits. Although no formal inclusion criteria were applied, factors that influenced the decision to prescribe ARBs included evidence of a rapid rate of change in aortic-root diameter despite other medical therapy, including beta-blockers with or without ACE inhibitors (11 patients); an aortic-root diameter of at least 4.0 cm, approaching the threshold for surgical intervention (6 patients); and unacceptable adverse events associated with conventional pharmacologic agents (1 patient). Details of therapy before the initiation of ARB treatment are provided in the Supplementary Appendix.
We identified 65 additional pediatric patients with Marfan's syndrome who had undergone echocardiography at least three times at Johns Hopkins Hospital during the study period, had not had aortic-root surgery, and had not received ARB therapy. All patients in this cohort had received beta-blockers according to a dosing regimen similar to that used in the recipients of ARBs before the initiation of ARB therapy.
Therapy with ARBs
Therapy was initiated in 17 patients with the ARB losartan (Cozaar, Merck) at an initial oral dose of 0.6 mg per kilogram of body weight per day; therapy with ACE inhibitors or calcium-channel blockers was discontinued at this time. The patients were assessed for adverse events at this starting dose over a 3-week period before the dose was gradually increased to a sustained dose of 1.4 mg per kilogram per day. Therapy was initiated in one additional patient with the ARB irbesartan (Avapro, Bristol-Myers Squibb) at an initial dose of 1.4 mg per kilogram per day and a final dose of 2.0 mg per kilogram per day. The blood urea nitrogen and creatinine levels (i.e., renal function) and electrolyte levels were assessed after the patients had received ARB therapy for 3 months. Beta-blocker therapy was not decreased or discontinued unless the patient had adverse events in association with both medications (see the Supplementary Appendix).
Echocardiography
Two-dimensional transthoracic echocardiograms were obtained every 3 to 12 months as part of routine clinical care, with the use of transducers appropriate for the patient's size. Complete orthogonal sweeps from the subxiphoid, apical, parasternal, and suprasternal-notch windows were obtained during each study. Measurements of maximal aortic diameter were taken at the aortic annulus, sinotubular junction, ascending thoracic aorta, and aortic root at the sinuses of Valsalva with the use of a parasternal long-axis view. The maximal diameter of these segments was determined by measuring from internal edge to internal edge of the aortic wall during ventricular systole on an axis perpendicular to the path of blood flow.
All echocardiograms obtained at Johns Hopkins Hospital were read by attending cardiologists who were not involved in the study and who were unaware of the patient's treatment status. A subgroup of studies was performed on selected patients, and the results were interpreted at other institutions. The majority of the echocardiograms were reviewed at Johns Hopkins to ensure standardization of measurement practices.
A z score was calculated for each echocardiographic measurement with the use of standard algorithms. The z score represented the standard deviation from the mean aortic diameter normalized for the patient's body-surface area and age.14 In addition, measurements of heart rate, blood pressure, height, and weight were obtained at the time of each echocardiogram. Measurements of height and weight were used to calculate the body-mass index and were converted into z scores normalized for sex and age.
Statistical Analysis
The Wilcoxon signed-rank test was used to compare the rates of change in aortic diameter before and after the initiation of ARB therapy in individual patients. The one-sample proportion test (sign test) was used to test for a consistent decrease in the rate of change in aortic-root diameter after the initiation of ARB therapy, with a null hypothesis of equal proportions. Linear regression models were fitted with the use of generalized estimating equations15 with a breakpoint to compare the rates of aortic enlargement before and after the initiation of ARB therapy, after adjustment for age and sex. The last model takes into account the correlation between repeated measures within individual patients. The Mann–Whitney U test was used to compare the changes in absolute and normalized aortic-root diameter between patients treated with ARBs and those treated with beta-blockers alone. Two-sided P values of less than 0.05 were considered to indicate statistical significance for all statistical tests and models. Stata statistical software, version 9.0, was used for all analyses.
Results
Characteristics of Patients Receiving ARB Therapy
Demographic data, diagnostic criteria, and treatment information for the 18 pediatric patients receiving ARB therapy are given in Table 1Table 1
Characteristics of the 18 Patients Receiving ARB Therapy. (and in Table 1 in the Supplementary Appendix). All patients had evidence of severe aortic-root enlargement, with a mean (±SD) aortic-root diameter of 3.67±0.53 cm and a mean aortic-root-diameter z score of 7.21±2.69 at the time ARB therapy was initiated. The median duration of treatment before the initiation of ARB therapy was 48.6 months, with a median of seven echocardiograms per patient. The age at initiation of ARB therapy ranged from 14 months to 16 years. All patients were receiving the maximal weight-based dose within 6 months after the initiation of therapy. The patients were followed for a median of 26.1 months while receiving ARB therapy and had a median of five echocardiograms during that period.At the time of data analysis, two patients, both of whom had severe aortic-root enlargement at the time of initiation of ARB therapy (4.2 cm in one and 4.4 cm in the other), had undergone previously planned prophylactic aortic-root replacement when their aortic-root diameter reached approximately 4.5 cm. A third patient required mitral-valve repair because of valve insufficiency and left ventricular dysfunction. The data for these three patients were censored at the time of surgery.
Side Effects
There were no significant changes in mean heart rate, mean systolic blood pressure, or mean diastolic blood pressure after the initiation of ARB therapy, as compared with the previous period when the patients were receiving beta-blockers, ACE inhibitors, or calcium-channel blockers (Table 2Table 2
Comparison of Hemodynamic Measurements before and after Initiation of ARB Therapy.). Laboratory indicators of renal function were normal 3 months after the initiation of ARB therapy in all patients: the median blood urea nitrogen level was 15 mg per deciliter (5.4 mmol per liter) (range, 7 to 25 mg per deciliter [2.5 to 8.9 mmol per liter]), and the median serum creatinine level was 0.5 mg per deciliter (44.2 μmol per liter) (range, 0.3 to 0.8 mg per deciliter [26.5 to 70.7 μmol per liter]). No adverse events or side effects were documented among patients while they were receiving ARB therapy.Body Height and Weight during ARB Therapy
There was a decline in the rate of change of increase in body height after the initiation of ARB therapy, with significant decreases in height velocity and in height-velocity z scores, as compared with previous growth rates (see Table 2 in the Supplementary Appendix). No significant changes were found in the rate of change in body-weight measurements. This finding might be attributable, at least in part, to a reduction in linear growth and age-dependent fluctuations in the rate of change in body-mass index.
Aortic-Root Dilation during ARB Therapy
The mean rate of change in aortic-root diameter in patients before the initiation of ARB therapy was 3.54±2.87 mm per year. After the initiation of ARB therapy, this rate decreased to 0.46±0.62 mm per year, which represented a clinically and statistically significant difference in aortic dilatation (P<0.001) (Table 3Table 3
Comparison of Annual Rates of Change in Aortic-Root Diameter and z Scores in Patients with Severe Marfan's Syndrome before and after Initiation of ARB Therapy and in Patients with Mild Marfan's Syndrome Receiving Beta-Blockers Alone.). The mean and median rates of increase in aortic-root diameter were decreased by factors of approximately 8 and 11, respectively (Figure 1AFigure 1Mean Annual Rate of Change in Absolute and Normalized Aortic Diameters before and after Initiation of Therapy with an Angiotensin II–Receptor Blocker (ARB). and Table 3). Similarly, the mean rate of change in aortic-root-diameter z scores was 0.97±1.55 per year before ARB therapy and decreased to −0.50±0.43 per year after the initiation of ARB therapy (P<0.001) (Table 3 and Figure 1B). The z score takes into account differences in age and body-surface area among patients and thus provides a measure that controls for the effects of these variables during follow-up.14 Regression modeling with the use of generalized estimating equations, after adjustment for age and sex, showed that the initiation of ARB therapy was independently associated with an estimated decrease in the rate of change in aortic-root diameter of 2.75 mm per year (95% confidence interval [CI], 1.65 to 3.84 mm per year; P<0.001) and an estimated decrease of 1.27 aortic-root-diameter z scores per year (95% CI, 0.57 to 1.97; P<0.001). The rate of change in aortic-root diameter was reduced among all patients after initiation of ARB therapy (P<0.001) (Figure 2AFigure 2
Change in Aortic-Root Diameter Standardized According to the Time of Initiation of Therapy with an Angiotensin II–Receptor Blocker (ARB)., and Table 1 in the Supplementary Appendix), including the single patient treated with irbesartan (Figure 2B).The sinotubular junction, an aortic segment that is also prone to dilation in patients with severe Marfan's syndrome, also benefited from ARB therapy. The mean rate of change in absolute sinotubular-junction diameter was 2.02±1.13 mm per year before the initiation of ARB therapy and was reduced to 0.70±1.01 mm per year during ARB therapy (P<0.05) (Table 4Table 4
Comparison of Annual Rates of Change in Aortic Diameter and z Scores before and after the Initiation of ARB Therapy. and Figure 1A). The normalized rate of sinotubular-junction enlargement decreased from 0.43±0.57 z score per year during previous therapy to −0.24±0.44 z score per year during ARB therapy (P<0.05) (Table 4 and Figure 1B). In comparison, more distal segments of the ascending aorta past the sinotubular junction, which are not generally affected by pathologic dilatation in Marfan's syndrome, showed no change in growth measurements after the initiation of ARB therapy. Both the mean rate of change in ascending-aorta diameter and the mean rate of change in ascending-aorta-diameter z score were essentially unchanged after the initiation of ARB therapy (Table 4). Finally, the rates of change in absolute aortic-annulus (aortic-valve) diameter and aortic-valve-diameter z score were also unaffected by the initiation of ARB therapy (Table 4).Aortic-Root Dilation during Treatment with Beta-Blockers Alone
Of the 65 patients with Marfan's syndrome who received beta-blocker therapy alone throughout the study period, 36 (55%) were female, 3 (5%) were black, and the median age was 12.0 years (range, 4 months to 19 years). Overall, this population had milder aortic-root disease, as evidenced by a reduced mean aortic-root-diameter z score for all echocardiograms obtained during childhood as compared with the mean z score of the cohort receiving ARB therapy (3.25±1.52 vs. 6.52±2.43, P<0.001). The mean rates of change in aortic-root diameter (1.71±1.24 mm per year) and in aortic-root-diameter z score (0.24±0.50 per year) in patients receiving beta-blockers alone were significantly higher than those in severely affected patients receiving ARB therapy (P<0.001 for both comparisons) (Table 3).
Discussion
The current study provides early evidence suggesting that the addition of losartan or another ARB to the traditional regimen used to treat aortic aneurysm in patients with Marfan's syndrome may be beneficial. The initiation of ARB therapy resulted in a significant reduction in the rate of change in aortic-root diameter as compared with beta-blocker therapy alone. The therapeutic effect extended to the sinotubular junction, a site also affected by Marfan's syndrome. In comparison, aortic segments not typically affected in Marfan's syndrome (e.g., the ascending aorta above the sinotubular junction) continued to show an annual rate of change in diameter that was appropriate for age and body size. Together, these findings suggest that ARBs do not arrest aortic growth but specifically reduce the pathologic rate of increase in the diameter of aortic segments that are already of sufficient size to accommodate the physiologic demands of the tissues for blood flow.
Losartan and irbesartan belong to the ARB class of antihypertensive medications that work by selectively blocking the angiotensin II type 1 (AT1) receptor within the renin–angiotensin–aldosterone system.16 In addition to antihypertensive and other effects, AT1-receptor blockade induces a clinically relevant decrease in TGF-β signaling.12,17,18 This antagonism results in reduced plasma levels of free TGF-β, reduced tissue expression of TGF-β–responsive genes, and reduced levels of intracellular mediators within the TGF-β signaling cascade, such as phosphorylated Smad2. In a prospective study of renal-transplant recipients, treatment with normal antihypertensive doses of losartan decreased plasma levels of TGF-β by more than 50% within 2 weeks.18
The effects of angiotensin II are mediated by two receptors, the AT1 receptor and the angiotensin II type 2 (AT2) receptor.16 AT1-receptor signaling can increase the production of TGF-β ligands and receptors, as well as activators such as thrombospondin-1.19 Cellular events observed in the tissues of persons with Marfan's syndrome, including proliferation of vascular smooth-muscle cells, fibrosis, and increased expression of matrix metalloproteinases 2 and 9, are plausibly attributable to increased TGF-β activity.8-10 In contrast, the AT2 receptor is thought to induce cellular effects opposite to those of the AT1 receptor, including antiproliferative and antiinflammatory effects that are beneficial in aortic-wall homeostasis.20
Given these mechanisms, the beneficial effects of ACE inhibitors and ARBs in this setting might be expected to differ. ACE inhibitors limit the production of angiotensin II and hence limit signaling through both the detrimental AT1-receptor pathway and the potentially protective AT2-receptor pathway and would not influence alternative mechanisms for angiotensin II production, such as the activity of mast-cell chymase. In contrast, ARBs cause selective blockade of the AT1 receptor, resulting in overactivation of the AT2-receptor pathway.10 In keeping with these mechanistic hypotheses, Daugherty and colleagues observed that AT1-receptor–blocking agents could prevent abdominal aortic aneurysms induced by the infusion of angiotensin II in apolipoprotein E–deficient mice, whereas selective AT2-receptor antagonists increased both the incidence and the severity of abdominal aneurysms in this model.21,22
On balance, however, it seems possible that the benefit of AT1-receptor antagonism achieved with ACE inhibitors could outweigh the potential negative influence of AT2-receptor blockade. A small, randomized, controlled trial of the ACE inhibitor perindopril as compared with placebo in adult patients with Marfan's syndrome who were receiving beta-blockers showed a reduced rate of change in aortic-root diameter that correlated with decreased circulating TGF-β levels over a relatively short period of follow-up (24 weeks).23 Nevertheless, our recent observation of accelerated aortic-root enlargement in fibrillin-1–deficient mice after targeted disruption of the gene encoding the AT2 receptor further supports our hypothesis that selective AT1-receptor antagonists will provide superior protection in preventing aneurysmal dilation of the aortic root (unpublished data).
There are several limitations of our study. This was a nonrandomized, retrospective, observational study that evaluated only a small subgroup of pediatric patients with Marfan's syndrome who had evidence of severe aortic-root enlargement or rapid increase in aortic diameter. Selection bias may have resulted in the identification of patients who were more adherent to, and therefore more likely to have a response to, ARB therapy, although it could also be hypothesized that patients with established severe disease would be less likely to have a response to ARB therapy than would patients with milder disease. Although all patients in this study had a reduction in the rate of change of aortic-root diameter while receiving ARB therapy, there was variability in this therapeutic response (Figure 2A, and Table 2 in the Supplementary Appendix) that may be correlated with the preexisting degree of pathologic change or other individually specific factors, such as genotype. This variability may alter the effectiveness of TGF-β antagonism, which was not assessed in this study. It is also possible that up-regulation of AT1 receptors in response to chronic receptor antagonism may limit the long-term therapeutic effect of ARBs.
Despite the encouraging results of this observational study, equipoise is maintained regarding a role for ARB therapy in the treatment of patients with Marfan's syndrome; our findings must be confirmed by a prospective, randomized trial. A trial coordinated by the Pediatric Heart Network of the National Heart, Lung, and Blood Institute, comparing losartan with atenolol in patients with Marfan's syndrome, began enrolling patients in the winter of 2007, and we encourage all eligible patients to enroll in this trial.24,25 Until data from this trial are available, evidence for the potential efficacy of ARB therapy in this setting should be considered preliminary.
Supported by a K12 Mentored Clinical Research Scholars Grant (to Dr. Brooke), as well as research grants from the National Institutes of Health (to Dr. Dietz), the Howard Hughes Medical Institute (to Drs. Dietz and Patel), the William S. Smilow Center for Marfan Syndrome Research (to Dr. Dietz), the Dana and Albert “Cubby” Broccoli Center for Aortic Diseases (to Drs. Dietz and Judge), and the National Marfan Foundation (to Drs. Dietz, Habashi, and Patel).
Dr. Loeys reports being a senior clinical investigator for the Fund for Scientific Research–Flanders.
No potential conflict of interest relevant to this article was reported.
We thank Gretchen Oswald, Jennifer Leadroot, and numerous clinicians throughout the United States for their help in gathering patient data, as well as Dr. Steven Piantadosi and Dr. Richard Thompson for their assistance in designing and executing the statistical analyses of this study.
Source Information
From the McKusick–Nathans Institute of Genetic Medicine and the Howard Hughes Medical Institute (B.S.B., J.P.H., N.P., B.L., H.C.D.), the Department of Surgery (B.S.B.), and the Department of Medicine and Cardiology (D.P.J.), Johns Hopkins University School of Medicine, Baltimore; and the Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium (B.L.).
Address reprint requests to Dr. Dietz at the McKusick–Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 539 Broadway Research Bldg., 733 N. Broadway, Baltimore, MD 21205, or at hdietz@jhmi.edu.
- References
References
1
Dietz HC ,Cutting GR ,Pyeritz RE , et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991;352:337-339
CrossRef | Web of Science | Medline2
Dietz HC ,Pyeritz RE . Mutations in the human gene for fibrillin-1 (FBN1) in the Marfan syndrome and related disorders. Hum Mol Genet 1995;4:1799-1809
Web of Science | Medline3
Milewicz DM ,Dietz HC ,Miller DC . Treatment of aortic disease in patients with Marfan syndrome. Circulation 2005;111:e150-e157
CrossRef | Web of Science | Medline4
Judge DP ,Dietz HC . Marfan syndrome. Lancet 2005;366:1965-1976
CrossRef | Web of Science | Medline5
Shores J ,Berger KR ,Murphy EA ,Pyeritz RE . Progression of aortic dilatation and the benefit of long-term β-adrenergic blockade in Marfan's syndrome. N Engl J Med 1994;330:1335-1341
Full Text | Web of Science | Medline6
Rossi-Foulkes R ,Roman MJ ,Rosen SE , et al. Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome. Am J Cardiol 1999;83:1364-1368
CrossRef | Web of Science | Medline7
Yetman AT ,Bornemeier RA ,McCrindle BW . Usefulness of enalapril versus propranolol or atenolol for prevention of aortic dilation in patients with the Marfan syndrome. Am J Cardiol 2005;95:1125-1127
CrossRef | Web of Science | Medline8
Ng CM ,Cheng A ,Myers LA , et al. TGF-β-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest 2004;114:1586-1592
Web of Science | Medline9
Neptune ER ,Frischmeyer PA ,Arking DE , et al. Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome. Nat Genet 2003;33:407-411
CrossRef | Web of Science | Medline10
Habashi JP ,Judge DP ,Holm TM , et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 2006;312:117-121
CrossRef | Web of Science | Medline11
Gelb BD . Marfan's syndrome and related disorders -- more tightly connected than we thought. N Engl J Med 2006;355:841-844
Full Text | Web of Science | Medline12
Lavoie P ,Robitaille G ,Agharazii M ,Ledbetter S ,Lebel M ,Lariviere R . Neutralization of transforming growth factor-beta attenuates hypertension and prevents renal injury in uremic rats. J Hypertens 2005;23:1895-1903
CrossRef | Web of Science | Medline13
De Paepe A ,Devereux RB ,Dietz HC ,Hennekam RC ,Pyeritz RE . Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996;62:417-426
CrossRef | Web of Science | Medline14
Sluysmans T ,Colan SD . Theoretical and empirical derivation of cardiovascular allometric relationships in children. J Appl Physiol 2005;99:445-457
CrossRef | Web of Science | Medline15
Zeger SL ,Liang KY . Longitudinal data analysis for discrete and continuous outcomes. Biometrics 1986;42:121-130
CrossRef | Web of Science | Medline16
Burnier M . Angiotensin II type 1 receptor blockers. Circulation 2001;103:904-912
Web of Science | Medline17
Lim DS ,Lutucuta S ,Bachireddy P , et al. Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation 2001;103:789-791
Web of Science | Medline18
Campistol JM ,Inigo P ,Larios S ,Bescos M ,Oppenheimer F . Role of transforming growth factor-beta 1 in the progression of chronic allograft nephropathy. Nephrol Dial Transplant 2001;16:Suppl 1:114-116
Web of Science | Medline19
Zhou Y ,Poczatek MH ,Berecek KH ,Murphy-Ullrich JE . Thrombospondin 1 mediates angiotensin II induction of TGF-beta activation by cardiac and renal cells under both high and low glucose conditions. Biochem Biophys Res Commun 2006;339:633-641
CrossRef | Web of Science | Medline20
Wu L ,Iwai M ,Nakagami H , et al. Roles of angiotensin II type 2 receptor stimulation associated with selective angiotensin II type 1 receptor blockade with valsartan in the improvement of inflammation-induced vascular injury. Circulation 2001;104:2716-2721
CrossRef | Web of Science | Medline21
Daugherty A ,Manning MW ,Cassis LA . Antagonism of AT2 receptors augments angiotensin II-induced abdominal aortic aneurysms and atherosclerosis. Br J Pharmacol 2001;134:865-870
CrossRef | Web of Science | Medline22
Daugherty A ,Rateri DL ,Cassis LA . Role of the renin-angiotensin system in the development of abdominal aortic aneurysms in animals and humans. Ann N Y Acad Sci 2006;1085:82-91
CrossRef | Web of Science | Medline23
Ahimastos AA ,Aggarwal A ,D'Orsa KM , et al. Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial. JAMA 2007;298:1539-1547
CrossRef | Web of Science | Medline24
Lacro RV ,Dietz HC ,Wruck LM , et al. Rationale and design of a randomized clinical trial of β-blocker therapy (atenolol) versus angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome. Am Heart J 2007;154:624-631
CrossRef | Web of Science | Medline25
Pediatric Heart Network. Marfan study basics. (Accessed June 2, 2008, at http://www.pediatricheartnetwork.org/marfanforhealthcareproviders.asp.)
- Citing Articles (117)
Citing Articles
1
2012. Case 44. , 140-142.
CrossRef2
Vijaya Joshi, Roxane McKay. 2012. Left Ventricular Outflow Regurgitation and Aortoventricular Tunnel. , 426-435.
CrossRef3
Matt Peter, Eckstein Friedrich. (2012) Novel pharmacological strategies to prevent aortic complications in Marfan syndrome. Journal of Geriatric Cardiology 8:4, 254-257
CrossRef4
David L. Rimoin, George E. Tiller. 2012. Skeletal Dysplasias and Connective Tissue Disorders. , 258-276.
CrossRef5
Yang Yang, Yi Cui, Dao-Quan Peng. (2012) ARB may be superior to ACEI on treatment of Marfan's syndrome by blocking TGF-β mediated activation of ERK. International Journal of Cardiology
CrossRef6
Ion S. Jovin, Mona Duggal, Keita Ebisu, Hyung Paek, A. Dana Oprea, Maryann Tranquilli, John Rizzo, Redin Memet, Marina Feldman, James Dziura, Cynthia A. Brandt, John A. Elefteriades. (2012) Comparison of the Effect on Long-Term Outcomes in Patients With Thoracic Aortic Aneurysms of Taking Versus Not Taking a Statin Drug. The American Journal of Cardiology
CrossRef7
Ilenia Foffa, Michele Murzi, Massimiliano Mariani, Anna Maria Mazzone, Mattia Glauber, Lamia Ait Ali, Maria Grazia Andreassi. (2012) Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves. The Journal of Thoracic and Cardiovascular Surgery
CrossRef8
Reed E. Pyeritz, Bart Loeys. (2012) The 8th international research symposium on the Marfan Syndrome and related conditions. American Journal of Medical Genetics Part A 158A:1, 42-49
CrossRef9
Thomas Doetschman, Joey V. Barnett, Raymond B. Runyan, Todd D. Camenisch, Ronald L. Heimark, Henk L. Granzier, Simon J. Conway, Mohamad Azhar. (2012) Transforming growth factor beta signaling in adult cardiovascular diseases and repair. Cell and Tissue Research 347:1, 203-223
CrossRef10
Christina M. Laukaitis. (2012) Genetics for the General Internist. The American Journal of Medicine 125:1, 7-13
CrossRef11
Toru Suzuki, Eric M. Isselbacher, Christoph A. Nienaber, Reed E. Pyeritz, Kim A. Eagle, Thomas T. Tsai, Jeanna V. Cooper, James L. Januzzi, Alan C. Braverman, Daniel G. Montgomery, Rossella Fattori, Linda Pape, Kevin M. Harris, Anna Booher, Jae K. Oh, Mark Peterson, Vijay S. Ramanath, James B. Froehlich. (2012) Type-Selective Benefits of Medications in Treatment of Acute Aortic Dissection (from the International Registry of Acute Aortic Dissection [IRAD]). The American Journal of Cardiology 109:1, 122-127
CrossRef12
Maria Luisa Bianchi, Francis H. Glorieux. 2012. The Spectrum of Pediatric Osteoporosis. , 439-509.
CrossRef13
Todd L. Kiefer, Andrew Wang, G. Chad Hughes, Thomas M. Bashore. (2011) Management of Patients With Bicuspid Aortic Valve Disease. Current Treatment Options in Cardiovascular Medicine 13:6, 489-505
CrossRef14
Marc-Phillip Hitz, Thomas Brand, Gregor Andelfinger. (2011) Genetic regulation of heart valve development: Clinical implications. Aswan Heart Centre Science & Practice Series 2011:2, 9
CrossRef15
Joshua D. Hutcheson, Vincent Setola, Bryan L. Roth, W. David Merryman. (2011) Serotonin receptors and heart valve disease—It was meant 2B. Pharmacology & Therapeutics 132:2, 146-157
CrossRef16
Sachin S. Goel, E. Murat Tuzcu, Shikhar Agarwal, Olcay Aksoy, Amar Krishnaswamy, Brian P. Griffin, Lars G. Svensson, Samir R. Kapadia. (2011) Comparison of Ascending Aortic Size in Patients With Severe Bicuspid Aortic Valve Stenosis Treated With Versus Without a Statin Drug. The American Journal of Cardiology 108:10, 1458-1462
CrossRef17
J Iwata, C Parada, Y Chai. (2011) The mechanism of TGF-β signaling during palate development. Oral Diseases 17:8, 733-744
CrossRef18
Y.C. Chan, R.E. Clough, P.R. Taylor. (2011) Predicting Aneurysmal Dilatation after Type B Aortic Dissection. European Journal of Vascular and Endovascular Surgery 42:4, 464-466
CrossRef19
Rohit Seth Loomba, Rohit R Arora. (2011) Role of angiotensin receptor blockers for management of aortic root dilation associated with Marfan syndrome. Expert Review of Cardiovascular Therapy 9:10, 1257-1259
CrossRef20
Hong-Shan Guan, Hai-Juan Shangguan, Zhuo Shang, Long Yang, Xian-Ming Meng, Shu-Bin Qiao. (2011) Endoplasmic Reticulum Stress Caused by Left Ventricular Hypertrophy in Rats: Effects of Telmisartan. The American Journal of the Medical Sciences 342:4, 318-323
CrossRef21
Dirk Hubmacher, Suneel S. Apte. (2011) Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function. Cellular and Molecular Life Sciences 68:19, 3137-3148
CrossRef22
Debra L. Rateri, Deborah A. Howatt, Jessica J. Moorleghen, Richard Charnigo, Lisa A. Cassis, Alan Daugherty. (2011) Prolonged Infusion of Angiotensin II in apoE−/− Mice Promotes Macrophage Recruitment with Continued Expansion of Abdominal Aortic Aneurysm. The American Journal of Pathology 179:3, 1542-1548
CrossRef23
A. Hagège. (2011) Recherche translationnelle : des exemples récents ouvrent la voie vers des thérapeutiques novatrices en cardiologie. Archives des Maladies du Coeur et des Vaisseaux - Pratique 2011:200, 12-15
CrossRef24
Linggen Gao, Xianliang Zhou, Lin Zhang, Dan Wen, Qian Chang, Yongbo Wu, Lizhong Sun, Rutai Hui. (2011) Factors Influencing Prognosis in Patients With Marfan Syndrome After Aortic Surgery. Journal of Cardiothoracic and Vascular Anesthesia 25:4, 625-631
CrossRef25
Toru Suzuki, Santi Trimarchi, Daigo Sawaki, Viviana Grassi, Elena Costa, Vincenzo Rampoldi, Ryozo Nagai, Kim Eagle. (2011) Circulating Transforming Growth Factor-Beta Levels in Acute Aortic Dissection. Journal of the American College of Cardiology 58:7, 775
CrossRef26
Thomas Krieg, Monique Aumailley. (2011) The extracellular matrix of the dermis: flexible structures with dynamic functions. Experimental Dermatology 20:8, 689-695
CrossRef27
Areeg H. El-Gharbawy, Gifty Bhat, Jaime E. Murillo, Beth L. Thurberg, Christoph Kampmann, Karl-Eugen Mengel, Priya S. Kishnani. (2011) Expanding the clinical spectrum of late-onset Pompe disease: Dilated arteriopathy involving the thoracic aorta, a novel vascular phenotype uncovered. Molecular Genetics and Metabolism 103:4, 362-366
CrossRef28
F. S. Collins. (2011) Reengineering Translational Science: The Time Is Right. Science Translational Medicine 3:90, 90cm17-90cm17
CrossRef29
Els Moltzer, Jeroen Essers, Joep H.M. van Esch, Jolien W. Roos-Hesselink, A.H. Jan Danser. (2011) The role of the renin–angiotensin system in thoracic aortic aneurysms: Clinical implications. Pharmacology & Therapeutics 131:1, 50-60
CrossRef30
Florian S Schoenhoff, Duke E Cameron, Gabor Matyas, Thierry P Carrel. (2011) Cardiovascular surgery in Marfan syndrome: implications of new molecular concepts in thoracic aortic disease. Future Cardiology 7:4, 557-569
CrossRef31
Denise van der Linde, Sing C. Yap, Arie P.J. van Dijk, Werner Budts, Petronella G. Pieper, Pieter H. van der Burgh, Barbara J.M. Mulder, Maarten Witsenburg, Judith A.A.E. Cuypers, Jan Lindemans, Johanna J.M. Takkenberg, Jolien W. Roos-Hesselink. (2011) Effects of Rosuvastatin on Progression of Stenosis in Adult Patients With Congenital Aortic Stenosis (PROCAS Trial). The American Journal of Cardiology 108:2, 265-271
CrossRef32
Alain Li-Wan-Po, Bart Loeys, Peter Farndon, David Latham, Caroline Bradley. (2011) Preventing the aortic complications of Marfan syndrome: a case-example of translational genomic medicine. British Journal of Clinical Pharmacology 72:1, 6-17
CrossRef33
Anna M. Booher, Kim A. Eagle. (2011) Diagnosis and management issues in thoracic aortic aneurysm. American Heart Journal 162:1, 38-46.e1
CrossRef34
Marc Lacour. 2011. Buschke-Ollendorff Syndrome, Marfan Syndrome, Osteogenesis Imperfecta, Anetodermas and Atrophodermas. , 145.1-145.21.
CrossRef35
Christopher P Barnett, David Chitayat, Timothy J Bradley, Yanting Wang, Aleksander Hinek. (2011) Dexamethasone normalizes aberrant elastic fiber production and collagen 1 secretion by Loeys–Dietz syndrome fibroblasts: a possible treatment?. European Journal of Human Genetics 19:6, 624-633
CrossRef36
Cristina Gavilán, Ignacio Herraiz, Miguel A. Granados, María T. Moral, Enery Gómez-Montes, Alberto Galindo. (2011) Prenatal diagnosis of neonatal Marfan syndrome. Prenatal Diagnosis 31:6, 610-613
CrossRef37
Alexandra F. Freeman, Elizabeth Mannino Avila, Pamela A. Shaw, Joie Davis, Amy P. Hsu, Pamela Welch, Jatin R. Matta, Colleen Hadigan, Roderic I. Pettigrew, Steven M. Holland, Ahmed M. Gharib. (2011) Coronary Artery Abnormalities in Hyper-IgE Syndrome. Journal of Clinical Immunology 31:3, 338-345
CrossRef38
Alberto Forteza, Arturo Evangelista, Violeta Sánchez, Gisela Teixidó, Diana García, Paz Sanz, Laura Gutiérrez, Jorge Centeno, José Rodríguez-Palomares, José Cortina, David García-Dorado. (2011) Valoración de la eficacia y la seguridad del losartán frente al atenolol en la prevención de la dilatación de la aorta en el síndrome de Marfan. Revista Española de Cardiología 64:6, 492-498
CrossRef39
Alberto Forteza, Arturo Evangelista, Violeta Sánchez, Gisela Teixidó, Diana García, Paz Sanz, Laura Gutiérrez, Jorge Centeno, José Rodríguez-Palomares, José Cortina, David García-Dorado. (2011) Study of the Efficacy and Safety of Losartan Versus Atenolol for Aortic Dilation in Patients With Marfan Syndrome. Revista Española de Cardiología (English Edition) 64:6, 492-498
CrossRef40
Mark E. Lindsay, Harry C. Dietz. (2011) Lessons on the pathogenesis of aneurysm from heritable conditions. Nature 473:7347, 308-316
CrossRef41
M McAllister, AM Wood, G Dunn, S Shiloh, C Todd. (2011) The Genetic Counseling Outcome Scale: a new patient-reported outcome measure for clinical genetics services. Clinical Genetics 79:5, 413-424
CrossRef42
J. P. Habashi, J. J. Doyle, T. M. Holm, H. Aziz, F. Schoenhoff, D. Bedja, Y. Chen, A. N. Modiri, D. P. Judge, H. C. Dietz. (2011) Angiotensin II Type 2 Receptor Signaling Attenuates Aortic Aneurysm in Mice Through ERK Antagonism. Science 332:6027, 361-365
CrossRef43
Klaus D. Hagspiel, Hugo Bonatti, Saher Sabri, Bulent Arslan, Nancy L. Harthun. (2011) Metachronous Bilateral Posterior Tibial Artery Aneurysms in Ehlers-Danlos Syndrome Type IV. CardioVascular and Interventional Radiology 34:2, 413-418
CrossRef44
Robert B. Hinton, Katherine E. Yutzey. (2011) Heart Valve Structure and Function in Development and Disease. Annual Review of Physiology 73:1, 29-46
CrossRef45
Cristina M. Alvira, Christophe Guignabert, Yu-Mee Kim, Chihhsin Chen, Lingli Wang, Trang T. Duong, Rae S.M. Yeung, Dean Y. Li, Marlene Rabinovitch. (2011) Inhibition of Transforming Growth Factor β Worsens Elastin Degradation in a Murine Model of Kawasaki Disease. The American Journal of Pathology 178:3, 1210-1220
CrossRef46
B. Diop-Frimpong, V. P. Chauhan, S. Krane, Y. Boucher, R. K. Jain. (2011) Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. Proceedings of the National Academy of Sciences 108:7, 2909-2914
CrossRef47
Eric D. Green, Mark S. Guyer, Eric D. Green, Mark S. Guyer, Teri A. Manolio, Jane L. Peterson. (2011) Charting a course for genomic medicine from base pairs to bedside. Nature 470:7333, 204-213
CrossRef48
Aaron L. Zuckerberg, Myron Yaster. 2011. Anesthesia for Orthopedic Surgery. , 842-869.
CrossRef49
Alberto Milan, Francesco Tosello, Mimma Caserta, Diego Naso, Elisabetta Puglisi, Corrado Magnino, Chiara Comoglio, Franco Rabbia, Paolo Mulatero, Franco Veglio. (2011) Aortic size index enlargement is associated with central hemodynamics in essential hypertension. Hypertension Research 34:1, 126-132
CrossRef50
Carlos Zaragoza, Carmen Gomez-Guerrero, Jose Luis Martin-Ventura, Luis Blanco-Colio, Begoña Lavin, Beñat Mallavia, Carlos Tarin, Sebastian Mas, Alberto Ortiz, Jesus Egido. (2011) Animal Models of Cardiovascular Diseases. Journal of Biomedicine and Biotechnology 2011, 1-13
CrossRef51
Gretchen J. Mahler, Jonathan T. Butcher. (2011) Inflammatory Regulation of Valvular Remodeling: The Good(?), the Bad, and the Ugly. International Journal of Inflammation 2011, 1-13
CrossRef52
Osamu Onodera. (2011) TGF-β family signaling contributes to human cerebral small vessel disease. Rinsho Shinkeigaku 51:11, 943-944
CrossRef53
H. Nistala, S. Lee-Arteaga, L. Carta, J. R. Cook, S. Smaldone, G. Siciliano, A. N. Rifkin, H. C. Dietz, D. B. Rifkin, F. Ramirez. (2010) Differential effects of alendronate and losartan therapy on osteopenia and aortic aneurysm in mice with severe Marfan syndrome. Human Molecular Genetics 19:24, 4790-4798
CrossRef54
Woo-In Yang, Chi-Young Shim, In-Jeong Cho, Hyuk-Jae Chang, Donghoon Choi, Yangsoo Jang, Namsik Chung, Seung-Yun Cho, Jong-Won Ha. (2010) Dyssynchronous Systolic Expansion of Carotid Artery in Patients with Marfan Syndrome. Journal of the American Society of Echocardiography 23:12, 1310-1316
CrossRef55
Kim L. McBride, Vidu Garg. (2010) Impact of Mendelian inheritance in cardiovascular disease. Annals of the New York Academy of Sciences 1214:1, 122-137
CrossRef56
Romain Debret, Valérie Cenizo, Géraldine Aimond, Valérie André, Martine Devillers, Isabelle Rouvet, André Mégarbané, Odile Damour, Pascal Sommer. (2010) Epigenetic Silencing of Lysyl Oxidase-Like-1 through DNA Hypermethylation in an Autosomal Recessive Cutis Laxa Case. Journal of Investigative Dermatology 130:11, 2594-2601
CrossRef57
Kim-Thanh Ong, Jérôme Perdu, Julie De Backer, Erwan Bozec, Patrick Collignon, Joseph Emmerich, Anne-Laure Fauret, Jean-Noël Fiessinger, Dominique P Germain, Gabriella Georgesco, Jean-Sebastien Hulot, Anne De Paepe, Henri Plauchu, Xavier Jeunemaitre, Stéphane Laurent, Pierre Boutouyrie. (2010) Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. The Lancet 376:9751, 1476-1484
CrossRef58
Milton Hamblin, Lin Chang, Hengmin Zhang, Kun Yang, Jifeng Zhang, Y. Eugene Chen. (2010) Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ deletion promotes abdominal aortic aneurysms. Journal of Vascular Surgery 52:4, 984-993
CrossRef59
F. Alpendurada, J. Wong, A. Kiotsekoglou, W. Banya, A. Child, S. K. Prasad, D. J. Pennell, R. H. Mohiaddin. (2010) Evidence for Marfan cardiomyopathy. European Journal of Heart Failure 12:10, 1085-1091
CrossRef60
H. Nistala, S. Lee-Arteaga, S. Smaldone, G. Siciliano, L. Carta, R. N. Ono, G. Sengle, E. Arteaga-Solis, R. Levasseur, P. Ducy, L. Y. Sakai, G. Karsenty, F. Ramirez. (2010) Fibrillin-1 and -2 differentially modulate endogenous TGF- and BMP bioavailability during bone formation. The Journal of Cell Biology 190:6, 1107-1121
CrossRef61
D. Detaint, L. Faivre, G. Collod-Beroud, A. H. Child, B. L. Loeys, C. Binquet, E. Gautier, E. Arbustini, K. Mayer, M. Arslan-Kirchner, C. Stheneur, D. Halliday, C. Beroud, C. Bonithon-Kopp, M. Claustres, H. Plauchu, P. N. Robinson, A. Kiotsekoglou, J. De Backer, L. Ades, U. Francke, A. De Paepe, C. Boileau, G. Jondeau. (2010) Cardiovascular manifestations in men and women carrying a FBN1 mutation. European Heart Journal 31:18, 2223-2229
CrossRef62
D. P. Judge. (2010) One step closer to personalized genomic medicine. European Heart Journal 31:18, 2194-2196
CrossRef63
Dustin Baldridge, Oleg Shchelochkov, Brian Kelley,, Brendan Lee. (2010) Signaling Pathways in Human Skeletal Dysplasias. Annual Review of Genomics and Human Genetics 11:1, 189-217
CrossRef64
A. Evangelista, F. A. Flachskampf, R. Erbel, F. Antonini-Canterin, C. Vlachopoulos, G. Rocchi, R. Sicari, P. Nihoyannopoulos, J. Zamorano, , , M. Pepi, O.-A. Breithardt, E. Plonska-Gosciniak. (2010) Echocardiography in aortic diseases: EAE recommendations for clinical practice. European Journal of Echocardiography 11:8, 645-658
CrossRef65
Feero, W. Gregory, Guttmacher, Alan E., , Dietz, Harry C., . (2010) New Therapeutic Approaches to Mendelian Disorders. New England Journal of Medicine 363:9, 852-863
Full Text66
Deepa Kabirdas, Cristiana Scridon, Juan-Carlos Brenes, Adrian V. Hernandez, Gian M. Novaro, Craig R. Asher. (2010) Accuracy of Transthoracic Echocardiography for the Measurement of the Ascending Aorta: Comparison With Transesophageal Echocardiography. Clinical Cardiology 33:8, 502-507
CrossRef67
Loren F. Hiratzka, George L. Bakris, Joshua A. Beckman, Robert M. Bersin, Vincent F. Carr, Donald E. Casey, Kim A. Eagle, Luke K. Hermann, Eric M. Isselbacher, Ella A. Kazerooni, Nicholas T. Kouchoukos, Bruce W. Lytle, Dianna M. Milewicz, David L. Reich, Souvik Sen, Julie A. Shinn, Lars G. Svensson, David M. Williams, Alice K. Jacobs, Sidney C. Smith, Jeffery L. Anderson, Cynthia D. Adams, Christopher E. Buller, Mark A. Creager, Steven M. Ettinger, Robert A. Guyton, Jonathan L. Halperin, Sharon A. Hunt, Harlan M. Krumholz, Frederick G. Kushner, Bruce W. Lytle, Rick Nishimura, Richard L. Page, Barbara Riegel, William G. Stevenson, Lynn G. Tarkington, Clyde W. Yancy. (2010) 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: Executive Summary. Catheterization and Cardiovascular Interventions 76:2, E43-E86
CrossRef68
Jason R. Cook, Harikiran Nistala, Francesco Ramirez. (2010) Drug-Based Therapies for Vascular Disease in Marfan Syndrome: From Mouse Models to Human Patients. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine 77:4, 366-373
CrossRef69
Gerard Tromp, Helena Kuivaniemi, Irene Hinterseher, David J. Carey. (2010) Novel Genetic Mechanisms for Aortic Aneurysms. Current Atherosclerosis Reports 12:4, 259-266
CrossRef70
Samuel C. Siu, Candice K. Silversides. (2010) Bicuspid Aortic Valve Disease. Journal of the American College of Cardiology 55:25, 2789-2800
CrossRef71
Christine B. Kern, Andy Wessels, Jessica McGarity, Laura J. Dixon, Ebony Alston, W. Scott Argraves, Danielle Geeting, Courtney M. Nelson, Donald R. Menick, Suneel S. Apte. (2010) Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies. Matrix Biology 29:4, 304-316
CrossRef72
Nigishi Hotta. (2010) Is there a place for inhibition of transforming growth factor-β and the polyol pathway in therapy for diabetic retinopathy?. Journal of Diabetes Investigationno-no
CrossRef73
S. M. Haldar, Y. Lu, D. Jeyaraj, D. Kawanami, Y. Cui, S. J. Eapen, C. Hao, Y. Li, Y. Q. Doughman, M. Watanabe, K. Shimizu, H. Kuivaniemi, J. Sadoshima, K. B. Margulies, T. P. Cappola, M. K. Jain. (2010) Klf15 Deficiency Is a Molecular Link Between Heart Failure and Aortic Aneurysm Formation. Science Translational Medicine 2:26, 26ra26-26ra26
CrossRef74
Loren F. Hiratzka, George L. Bakris, Joshua A. Beckman, Robert M. Bersin, Vincent F. Carr, Donald E. Casey, Kim A. Eagle, Luke K. Hermann, Eric M. Isselbacher, Ella A. Kazerooni, Nicholas T. Kouchoukos, Bruce W. Lytle, Dianna M. Milewicz, David L. Reich, Souvik Sen, Julie A. Shinn, Lars G. Svensson, David M. Williams. (2010) 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease. Journal of the American College of Cardiology 55:14, e27-e129
CrossRef75
Loren F. Hiratzka, George L. Bakris, Joshua A. Beckman, Robert M. Bersin, Vincent F. Carr, Donald E. Casey, Kim A. Eagle, Luke K. Hermann, Eric M. Isselbacher, Ella A. Kazerooni, Nicholas T. Kouchoukos, Bruce W. Lytle, Dianna M. Milewicz, David L. Reich, Souvik Sen, Julie A. Shinn, Lars G. Svensson, David M. Williams. (2010) 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: Executive Summary. Journal of the American College of Cardiology 55:14, 1509-1544
CrossRef76
Victoria Cañadas, Isidre Vilacosta, Isidoro Bruna, Valentin Fuster. (2010) Marfan syndrome. Part 2: treatment and management of patients. Nature Reviews Cardiology
CrossRef77
Alan Daugherty, Debra L. Rateri, Israel F. Charo, A. Phillip Owens, Deborah A. Howatt, Lisa A. Cassis. (2010) Angiotensin II infusion promotes ascending aortic aneurysms: attenuation by CCR2 deficiency in apoE −/− mice. Clinical Science 118:11, 681-689
CrossRef78
Aravinda Chakravarti. (2010) 2008 Presidential Address: Principia Genetica: Our Future Science. The American Journal of Human Genetics 86:3, 302-308
CrossRef79
John A. Elefteriades, Emily A. Farkas. (2010) Thoracic Aortic Aneurysm. Journal of the American College of Cardiology 55:9, 841-857
CrossRef80
Candice K. Silversides, Marla Kiess, Luc Beauchesne, Timothy Bradley, Michael Connelly, Koichiro Niwa, Barbara Mulder, Gary Webb, Jack Colman, Judith Therrien. (2010) Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: Outflow tract obstruction, coarctation of the aorta, tetralogy of Fallot, Ebstein anomaly and Marfan's syndrome. Canadian Journal of Cardiology 26:3, e80-e97
CrossRef81
Harry C. Dietz. (2010) TGF-β in the pathogenesis and prevention of disease: a matter of aneurysmic proportions. Journal of Clinical Investigation 120:2, 403-406
CrossRef82
John G.T. Augoustides, Michael Andritsos. (2010) Innovations in Aortic Disease: The Ascending Aorta and Aortic Arch. Journal of Cardiothoracic and Vascular Anesthesia 24:1, 198-207
CrossRef83
Francesco Ramirez, Lynn Y. Sakai. (2010) Biogenesis and function of fibrillin assemblies. Cell and Tissue Research 339:1, 71-82
CrossRef84
Kenju Hara. (2010) Molecular mechanism and therapeutic strategy for cerebral small vessel disease. Rinsho Shinkeigaku 50:11, 852-854
CrossRef85
Ruth Curry, Lorna Swan, Philip J Steer. (2009) Cardiac disease in pregnancy. Current Opinion in Obstetrics and Gynecology 21:6, 508-513
CrossRef86
Ismail El-Hamamsy, Magdi H. Yacoub. (2009) Cellular and molecular mechanisms of thoracic aortic aneurysms. Nature Reviews Cardiology 6:12, 771-786
CrossRef87
Zsolt Urban, Vishwanathan Hucthagowder, Nura Schürmann, Vesna Todorovic, Lior Zilberberg, Jiwon Choi, Carla Sens, Chester W. Brown, Robin D. Clark, Kristen E. Holland, Michael Marble, Lynn Y. Sakai, Branka Dabovic, Daniel B. Rifkin, Elaine C. Davis. (2009) Mutations in LTBP4 Cause a Syndrome of Impaired Pulmonary, Gastrointestinal, Genitourinary, Musculoskeletal, and Dermal Development. The American Journal of Human Genetics 85:5, 593-605
CrossRef88
Jonathan Golledge, Paul E Norman. (2009) Pathophysiology of abdominal aortic aneurysm relevant to improvements in patientsʼ management. Current Opinion in Cardiology 24:6, 532-538
CrossRef89
HH Clarice Yang, Jong Moo Kim, Elliott Chum, Cornelis van Breemen, Ada WY Chung. (2009) Long-term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndrome. British Journal of Pharmacology 158:6, 1503-1512
CrossRef90
Alberto Mazza, Stefano Cuppini, Sergio Zamboni, Laura Schiavon, Luca Zattoni, Andrea Viale, Francesco Corbetti, Roberta Ravenni, Alberto Sacco, Edoardo Casiglia. (2009) Does treatment with olmesartan improve arterial stenoses due to fibromuscular dysplasia?. Hypertension Research 32:10, 927-929
CrossRef91
Francesco Ramirez, Daniel B Rifkin. (2009) Extracellular microfibrils: contextual platforms for TGFβ and BMP signaling. Current Opinion in Cell Biology 21:5, 616-622
CrossRef92
Samuel J Lacina. (2009) Whatʼs new in outpatient cardiology. Current Opinion in Pediatrics 21:5, 605-610
CrossRef93
Daniel G. Tang, Michael D. Dake. (2009) TEVAR for Acute Uncomplicated Aortic Dissection: Immediate Repair Versus Medical Therapy. Seminars in Vascular Surgery 22:3, 145-151
CrossRef94
Natasha Shur, Dianne Abuelo. (2009) Genetic Syndromes: From Clinical Suspicion to Referral to Diagnosis. Pediatric Annals 38:8, 419-425
CrossRef95
John G.T. Augoustides, Yanika Wolfe, Elizabeth K. Walsh, Wilson Y. Szeto. (2009) Recent Advances in Aortic Valve Disease: Highlights From a Bicuspid Aortic Valve to Transcatheter Aortic Valve Replacement. Journal of Cardiothoracic and Vascular Anesthesia 23:4, 569-576
CrossRef96
Christopher Barnett, Jacob C. Langer, Aleksander Hinek, Timothy J. Bradley, David Chitayat. (2009) Looking past the lump: genetic aspects of inguinal hernia in children. Journal of Pediatric Surgery 44:7, 1423-1431
CrossRef97
Brian Hon-Yin Chung, Stephen Tak-Sum Lam, Tony Ming-For Tong, Susanna Yuk-Han Li, Kin-Shing Lun, Daniel Hon-Chuen Chan, Susanna Fung-Shan Fok, June Siu-Fong Or, David Keith Smith, Wanling Yang, Yu-Lung Lau. (2009) Identification of novel FBN1 and TGFBR2 mutations in 65 probands with Marfan syndrome or Marfan-like phenotypes. American Journal of Medical Genetics Part A 149A:7, 1452-1459
CrossRef98
Ralph AH Stewart. (2009) Clinical trials in heart valve disease. Current Opinion in Cardiology 24:4, 279-287
CrossRef99
Massimo Lombardi. (2009) Do we need a new syndrome within the heterogeneity of bicuspid aortic valve patients?. Journal of Cardiovascular Medicine 10:6, 443-445
CrossRef100
Fredrick M. Wigley. (2009) Vascular Disease in Scleroderma. Clinical Reviews in Allergy & Immunology 36:2-3, 150-175
CrossRef101
Richard N. Re. (2009) New Insights into Target Organ Involvement in Hypertension. Medical Clinics of North America 93:3, 559-567
CrossRef102
Delphine Gomez, Ayman Al Haj Zen, Luciano F Borges, Monique Philippe, Paulo Sampaio Gutierrez, Guillaume Jondeau, Jean-Baptiste Michel, Roger Vranckx. (2009) Syndromic and non-syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway. The Journal of Pathology 218:1, 131-142
CrossRef103
Toshio Takayama, Tetsuro Miyata, Hirokazu Nagawa. (2009) True abdominal aortic aneurysm in Marfan syndrome. Journal of Vascular Surgery 49:5, 1162-1165
CrossRef104
Jun Iwanami, Masaki Mogi, Masaru Iwai, Masatsugu Horiuchi. (2009) Inhibition of the renin–angiotensin system and target organ protection. Hypertension Research 32:4, 229-237
CrossRef105
Venu Menon, Jay Sengupta, Samuel Unzek. (2009) Optimal management of acute aortic dissection. Current Treatment Options in Cardiovascular Medicine 11:2, 146-155
CrossRef106
Fabiana I Gambarin, Valentina Favalli, Alessandra Serio, Mario Regazzi, Michele Pasotti, Catherine Klersy, Roberto Dore, Savina Mannarino, Mario Viganò, Attilio Odero, Simona Amato, Luigi Tavazzi, Eloisa Arbustini. (2009) Rationale and design of a trial evaluating the effects of losartan vs. nebivolol vs. the association of both on the progression of aortic root dilation in Marfan syndrome with FBN1 gene mutations. Journal of Cardiovascular Medicine 10:4, 354-362
CrossRef107
Paul Grossfeld, Maoqing Ye, Richard Harvey. (2009) Hypoplastic Left Heart Syndrome. Journal of the American College of Cardiology 53:12, 1072-1074
CrossRef108
John F. Bateman, Raymond P. Boot-Handford, Shireen R. Lamandé. (2009) Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations. Nature Reviews Genetics 10:3, 173-183
CrossRef109
J. De Backer, B. Loeys, A. De Paepe. (2009) Marfan and Marfan-like syndromes. Artery Research 3:1, 9-16
CrossRef110
Leandro Soriano-Guillén, Jesús Argente. (2009) Turner syndrome: prediction and treatment of cardiac events and aortic abnormalities. Pediatric Health 3:1, 19-24
CrossRef111
Marie-José Goumans, Zhen Liu, Peter ten Dijke. (2009) TGF-β signaling in vascular biology and dysfunction. Cell Research 19:1, 116-127
CrossRef112
Andrew E. Radbill, David W. Brown, Ronald V. Lacro, Frank Cecchin, Charles I. Berul, John K. Triedman, Laura M. Bevilacqua, Edward P. Walsh, Mark E. Alexander. (2008) Ascending aortic dilation in patients with congenital complete heart block. Heart Rhythm 5:12, 1704-1708
CrossRef113
(2008) Notable advances in the clinic. Nature Medicine 14:12, 1303-1303
CrossRef114
Carolyn A Bondy. (2008) Aortic dissection in Turner syndrome. Current Opinion in Cardiology 23:6, 519-526
CrossRef115
(2008) Angiotensin II Blockade in Marfan's Syndrome. New England Journal of Medicine 359:16, 1732-1734
Full Text116
J. De Backer. (2008) The expanding cardiovascular phenotype of Marfan syndrome. European Journal of Echocardiography 10:2, 213-215
CrossRef117
Pyeritz, Reed E., . (2008) A Small Molecule for a Large Disease. New England Journal of Medicine 358:26, 2829-2831
Full Text
- Letters
