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Genetic Basis of Thoracic Aortic Aneurysms and Dissections: Focus on Smooth Muscle Cell Contractile Dysfunction

Published on Sep 1, 2008in Annual Review of Genomics and Human Genetics7.91
· DOI :10.1146/annurev.genom.8.080706.092303
Dianna M. Milewicz56
Estimated H-index: 56
(University of Texas at Austin),
Dongchuan Guo32
Estimated H-index: 32
(University of Texas at Austin)
+ 5 AuthorsHariyadarshi Pannu18
Estimated H-index: 18
(University of Texas at Austin)
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Abstract
Thoracic aortic aneurysms leading to type A dissections (TAAD) can be inherited in isolation or in association with genetic syndromes, such as Marfan syndrome and Loeys-Dietz syndrome. When TAAD occurs in the absence of syndromic features, it is inherited in an autosomal dominant manner with decreased penetrance and variable expression, the disease is referred to as familial TAAD. Familial TAAD exhibits significant clinical and genetic heterogeneity. The first genes identified to cause TAAD were FBN1, TGFBR2, and TGFBR1. The identification and characterization of these genes suggested that increased TGF-β signaling plays a role in pathogenesis. The recent discovery that mutations in the vascular smooth muscle cell (SMC)-specific β-myosin (MYH11) and α-actin (ACTA2) can also cause this disorder has focused attention on the importance of the maintenance of SMC contractile function in preserving aortic structure and preventing TAAD.
  • References (97)
  • Citations (258)
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References97
Newest
Published on Jan 1, 2008in Journal of Vascular Surgery3.24
Wanfen Xiong15
Estimated H-index: 15
(UNMC: University of Nebraska Medical Center),
Rebecca Knispel7
Estimated H-index: 7
(UNMC: University of Nebraska Medical Center)
+ 2 AuthorsB. Timothy Baxter29
Estimated H-index: 29
(UNMC: University of Nebraska Medical Center)
Objectives Thoracic aneurysms are the main cardiovascular complication of Marfan syndrome (MFS) resulting in premature death. MFS has been associated with mutations of the gene encoding fibrillin-1 (FBN1), a major constituent of the elastic fibers. Matrix metalloproteinases (MMPs) are important in the pathogenesis of abdominal aortic aneurysms but their precise role in MFS is not clear. Doxycycline is a nonspecific MMP inhibitor. The objective of the study was to determine whether docycycline ca...
Published on Dec 1, 2007in Nature Genetics25.45
Dongchuan Guo32
Estimated H-index: 32
(University of Texas Health Science Center at Houston),
Hariyadarshi Pannu18
Estimated H-index: 18
(University of Texas Health Science Center at Houston)
+ 22 AuthorsElizabeth Sparks21
Estimated H-index: 21
(OSU: Ohio State University)
Mutations in smooth muscle α-actin ( ACTA2 ) lead to thoracic aortic aneurysms and dissections
Published on Oct 1, 2007in American Heart Journal4.02
Ronald V. Lacro28
Estimated H-index: 28
(Harvard University),
Harry C. Dietz86
Estimated H-index: 86
(Johns Hopkins University)
+ 15 AuthorsStephen M. Paridon34
Estimated H-index: 34
(UPenn: University of Pennsylvania)
Background Cardiovascular disease, including aortic root dilation, dissection, and rupture, is the leading cause of mortality in patients with Marfan syndrome (MFS). The maximal aortic root diameter at the sinuses of Valsalva is considered the best predictor of adverse cardiovascular outcome. Although advances in therapy have improved life expectancy, affected individuals continue to suffer cardiovascular morbidity and mortality. Recent studies in an FBN1 -targeted mouse model of MFS with aortic...
Published on Sep 1, 2007in American Journal of Medical Genetics Part A2.20
Melissa L. Loscalzo6
Estimated H-index: 6
(USF: University of South Florida),
Denise Li-Meng Goh21
Estimated H-index: 21
+ 3 AuthorsHarry C. Dietz86
Estimated H-index: 86
(Johns Hopkins University)
The autosomal dominant inheritance of bicommissural aortic valve (BAV) (Online Mendelian Inheritance in Man #109730) in some families is well-documented; however, the inheritance of BAV with thoracic aortic aneurysm (TAA) is less clear. Whether the aneurysm is secondary to hemodynamic perturbation related to the valve abnormality or a primary manifestation of the disorder remains controversial. Guidelines are needed regarding the follow-up and treatment of these patients and their families. Thir...
Published on Aug 1, 2007in Nature Reviews Cardiology17.42
Hüseyin Ince31
Estimated H-index: 31
,
Christoph Nienaber80
Estimated H-index: 80
Diagnosis and medical care of most aortic pathologies is frequently the responsibility of cardiologists. With the emergence of endovascular interventions, it is, therefore, increasingly important for cardiologists to gain confidence in managing at least the most-frequent presentations of aortic disease. Here, Huseyin Ince and Christoph Nienaber review the etiology, pathophysiology and clinical management of patients with thoracic aortic aneurysm, in the context of the most recent literature.
Published on Apr 5, 2007in Human Molecular Genetics4.54
Hariyadarshi Pannu18
Estimated H-index: 18
,
Van Tran-Fadulu11
Estimated H-index: 11
+ 12 AuthorsAllan R. Brasier54
Estimated H-index: 54
(UTMB: University of Texas Medical Branch)
Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in 20% of cases. Familial TAAD is genetically heterogeneous and four loci have been mapped for this disease to date, including a locus at 16p for TAAD associated with patent ductus arteriosus (PDA). The defective gene at the 16p locus has recently been identified as the smooth muscle cell (SMC)-specific myosin heavy chain gene (MYH11). On sequencing MYH11 in 93 families with TAAD alone a...
Published on Mar 1, 2007in Nature Reviews Cardiology17.42
Scott A. LeMaire47
Estimated H-index: 47
(BCM: Baylor College of Medicine),
Hariyadarshi Pannu18
Estimated H-index: 18
(University of Texas Health Science Center at Houston)
+ 3 AuthorsDianna M. Milewicz56
Estimated H-index: 56
Background A 24-year-old man presented with previously diagnosed Marfan’s syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or ...
Published on Jan 1, 2007in The Cardiology1.56
Ioannis Hatzaras5
Estimated H-index: 5
(Yale University),
Maryann Tranquilli20
Estimated H-index: 20
(Yale University)
+ 3 AuthorsJohn A. Elefteriades54
Estimated H-index: 54
(Yale University)
Background/Aims: In 2003, we reported on a small number of patients in whom acute aortic dissection appeared to be causally related to intense weight lifting. If additional cases co
Published on Dec 1, 2006in Cardiovascular Research7.01
Vishal Gupta10
Estimated H-index: 10
(Rice University),
Grande-Allen Jane31
Estimated H-index: 31
(Rice University)
Extracellular matrix (ECM) provides several structural and functional characteristics to tissues including cell support, mechanical integrity and biological signaling. In cardiovascular tissues, cells produce various ECM components such as collagen, elastin, proteoglycans, matrix metalloproteinases, growth factors and signaling molecules. The cardiovascular cells (cardiac fibroblasts, cardiomyocytes, endothelial cells, and vascular smooth muscle cells) sense the changes in mechanical strains app...
Published on Aug 24, 2006in The New England Journal of Medicine70.67
Bart Loeys56
Estimated H-index: 56
(UGent: Ghent University),
Ulrike Schwarze30
Estimated H-index: 30
(UW: University of Washington)
+ 18 AuthorsSylvie Manouvrier18
Estimated H-index: 18
(Lille University of Science and Technology)
Background The Loeys–Dietz syndrome is a recently described autosomal dominant aortic-aneurysm syndrome with widespread systemic involvement. The disease is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is caused by heterozygous mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2, respectively). Methods We undertook the clinical and molecular characterization of 52 affected familie...
Cited By258
Newest
Published on May 2, 2019in Scientific Reports4.01
Natalija Bogunovic2
Estimated H-index: 2
(VUmc: VU University Medical Center),
Jorn P. Meekel1
Estimated H-index: 1
(VUmc: VU University Medical Center)
+ 3 AuthorsKak K. Yeung8
Estimated H-index: 8
(VUmc: VU University Medical Center)
Ruptured abdominal aortic aneurysms (AAA) are associated with overall mortality rates up to 90%. Despite extensive research, mechanisms leading to AAA formation and advancement are still poorly understood. Smooth muscle cells (SMC) are predominant in the aortic medial layer and maintain the wall structure. Apoptosis of SMC is a well-known phenomenon in the pathophysiology of AAA. However, remaining SMC function is less extensively studied. The aim of this study is to assess the in vitro contract...
Rūta Krikščiūnienė (Lithuanian University of Health Sciences), Inesa Navickaitė (Lithuanian University of Health Sciences)+ -3 AuthorsRasa Verkauskienė5
Estimated H-index: 5
(Lithuanian University of Health Sciences)
Introduction. Turner syndrome (TS) is assigned to the rare diseases group. Morbidity and mortality of TS patients are high, particularly due to the cardiovascular disorders, so monitoring for cardiovascular complications must be ensured. The data demonstrate a strong correlation between 2-dimensional echocardiographic (2Decho) evaluation and magnetic resonance imaging (MRI); still, according to recent guidelines, MRI remains a gold standard. In this study, we aimed to compare aortic dimensions o...
Published on Aug 1, 2019in Computer Methods in Applied Mechanics and Engineering4.82
Nino Horvat , Lana Virag2
Estimated H-index: 2
+ 2 AuthorsIgor Karšaj9
Estimated H-index: 9
Abstract The general framework for growth and remodeling (G&R) of soft biological tissues shows a great potential for expanding our current understanding of biochemical and biomechanical processes, and to predict disease progression. Yet, its use is held up by the lack of a reliable and verified 3D finite element (FE) implementation capable of describing G&R processes of soft biological tissues. Thus, in this study we present the implementation of a 3D constrained mixture G&R model in a FE analy...
Published on Apr 2, 2019in International Journal of Stroke4.47
Jin-Yi Hsu , Yuan-Chih Su (PRC: China Medical University (PRC))+ 1 AuthorsBoon Lead Tee (UCSF: University of California, San Francisco)
BackgroundAneurysm of proximal thoracic aorta (pTAA) is an often indolent, yet fatal disease. Although advancements in aneurysmal repair techniques have increased long-term survival rates, studies have proven that there are increases in perioperative risk for stroke incidence after pTAA surgery. Conversely, there is little evidence regarding the long-term stroke incidence in pTAA individuals, which strongly influences the morbidity, mortality, and usage of antithrombotic agents.MethodsUsing the ...
Published on Mar 15, 2019in Clinical Science5.24
Fernando Pedro de Souza-Neto2
Estimated H-index: 2
(UFMG: Universidade Federal de Minas Gerais),
Mario de Morais e Silva1
Estimated H-index: 1
(UFMG: Universidade Federal de Minas Gerais)
+ 11 AuthorsMaria Claudia Irigoyen23
Estimated H-index: 23
(USP: University of São Paulo)
Aims: The renin–angiotensin system (RAS) plays an important role in the pathophysiology of vascular diseases, especially as a mediator of inflammation and tissue remodelling. Alamandine (Ala 1 -angiotensin-(1-7)) is a new biologically active peptide from the RAS, interacting with Mas-related G-protein-coupled receptor member D. Although a growing number of studies reveal the cardioprotective effects of alamandine, there is a paucity of data on its participation in vascular remodelling associated...
Published on Feb 15, 2019in Circulation Research15.86
Amélie Pinard1
Estimated H-index: 1
(University of Texas Health Science Center at Houston),
Gregory T. Jones30
Estimated H-index: 30
(University of Otago),
Dianna M. Milewicz56
Estimated H-index: 56
(University of Texas Health Science Center at Houston)
Alexander W. Caulk6
Estimated H-index: 6
(Yale University),
D HumphreyJay56
Estimated H-index: 56
(Yale University)
+ 0 AuthorsS.-I. Murtada1
Estimated H-index: 1
(Yale University)
Published on Jan 24, 2019in JCI insight
Christian Lacks Lino Cardenas10
Estimated H-index: 10
,
Chase W. Kessinger16
Estimated H-index: 16
+ 7 AuthorsFarouc A. Jaffer44
Estimated H-index: 44
Sina Stock4
Estimated H-index: 4
,
Salah A Mohamed14
Estimated H-index: 14
,
Hh Sievers34
Estimated H-index: 34
Bicuspid aortic valve related aortopathy is known to significantly increase the risk for catastrophic aortic events and, therefore, represents a considerable health burden. Albeit of ongoing research in this field including genetic, molecular, hemodynamic and morphologic aspects, bicuspid aortic valve related aortopathy still represents an imperfectly understood disorder. This lack in knowledge results in a lack of consistency considering different therapeutic approaches. Recent studies have pro...