Genetic Basis of Familial Valvular Heart Disease

Padang, Ratnasari; Bagnall, Richard D.; Semsarian, Christopher

doi:10.1161/circgenetics.112.962894

Cited by 42 publications

(46 citation statements)

References 100 publications

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“…A leading role in various mechanisms of pathogenesis of syndromic and non-syndromic MVP is played by the failure of TGF-β regulation [21,88]. TGF-β is a protein controlling a number of physiological processes including angiogenesis, proliferation, cellular differentiation and А.V.…”

Section: Molecular Biology and Genetics Of Mitral Valve Prolapsementioning

confidence: 99%

“…Marfan syndrome is associated with mutations in the FBN1 gene located on 15q15-q21 chromosome [85,90,101, 102], it may also be caused by mutation in gene TGF-β located on the 3p24.2-р25 chromosome [21,103]. The role of FBN1 and TGF-β mutation in MVP pathogenesis was confirmed by the experiment on mice with the model of Marfan syndrome [104].…”

Section: Molecular Biology and Genetics Of Mitral Valve Prolapsementioning

confidence: 99%

“…A leading mechanism disclosing a diverse MVP semiotics is vegetative dysfunction, though the availability of asymptomatic patients does not permit an unambiguous definition of its pathogenetic role [20,21]. Nevertheless, the majority of researchers [22][23][24] consider vegetative changes of homeostasis to be the obligate MVP manifestation.…”

Section: Diagnosis Of Mitral Valve Prolapsementioning

confidence: 99%

“…MVP is a pathology with genetic predisposition, which however does not occur in newborns [21,46], and is rarely observed in children (0.3%) [47] and young people (0.6%) [48]. These data convincingly characterize MVP as a progressing disease mainly affecting patients of middle years [1].…”

Section: Prevalence Of Mitral Valve Prolapsementioning

confidence: 99%

“…Among them are calcineurin stimulating the family of nuclear factors of activated T cells (NFAT), absence of which leads to the fatal valvular defects [82]; Wnt/β-catenin, determining the development of endothelial cells [83]; fibroblast growth factor FGF4; homeobox gene Sox4; modulator of transforming growth factor beta (TGF-β); superfamily of signaling proteins SMAD6 [84,85], the impaired work of which results in abnormal valve thickening. Defects in genes or signaling molecules may induce myxomatous valvular alterations and promote progressing impairment of their mechanical strength during life [86, 87].A leading role in various mechanisms of pathogenesis of syndromic and non-syndromic MVP is played by the failure of TGF-β regulation [21,88]. TGF-β is a protein controlling a number of physiological processes including angiogenesis, proliferation, cellular differentiation and А.V.…”

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confidence: 99%

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Mitral Valve Prolapse: Current Views and Challenges (Review)

Клеменов¹

2017

Sovrem Tehnol Med

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City Clinical Hospital No.30, 85а Beryozovskaya St., Nizhny Novgorod, 603157, Russian Federation Mitral valve prolapse (MVP) is the most common valve abnormality. Many issues relating its diagnosis, epidemiology, prognosis, and genetics have lately been defined more precisely or revised.The most principal changes in MVP diagnosis are connected with establishing a three-dimensional saddle-like shape of the mitral valve annulus, which made mandatory the assessment of the valve condition from the parasternal longitudinal position during ultrasound examination. Implementation of standard diagnostic criteria based on two-dimensional echocardiography, and making the results of the Framingham Heart Study public made it possible to overcome the contradictions relative to the prevalence of this pathology, which appeared to be lower than it had been considered earlier. Age, gender, and ethnic characteristics of MVP occurrence have been established. Notions not only about the incidence of mitral prolapse development but the severity of its sequelae were subjected to reassessment. If previously MVP was thought to be a disease with serious complications, findings of conducted epidemiological studies gave reasons to consider it as a benign pathology with a low probability of unfavorable consequences. Concurrently, factors of unfavorable prognosis were identified, and mitral regurgitation was recognized to be the main of them.The results of molecular genetic investigations enriched essentially notion about MVP and improved its diagnosing. At present, this pathology is believed to be a result of multiple genetic disorders caused by identification of several genes linked with the onset of syndromic prolapse, and three loci for nonsyndromic one. Creation of large-scale registers of MVP patients and conduction of genome-wide studies will enable cardiologists to identify new genes related to the emergence of mitral prolapse and provide screening of asymptomatic patients. The leading role in various mechanisms of MVP pathogenesis is played by the impairment of regulation of transforming growth factor beta (TGF-β), understanding of pathogenetic role of which opens new perspectives of conservative treatment of this pathology with the application of antibodies neutralizing TGF-β, and angiotensin II receptor blockers. Such medical approaches may be rather promising at the early stage of undiagnosed MVP phenotypes, and also serve as an alternative to surgical treatment of clinical complications in patients with a verified diagnosis.Key words: mitral valve prolapse; mitral prolapse diagnosing; MVP epidemiology; prognosis in prolapses; molecular and genetic basics in MVP; mitral regurgitation; transforming growth factor beta.For contacts: Aleksey V. Klemenov, e-mail: klemenov_av@list.ru А.V. KlemenovMitral valve prolapse (MVP) is the most common valve abnormality, which occurs in 2-3% of population [1][2][3][4][5]. This pathology is thought to be the leading cause of isolated mitral insufficiency demanding surgical intervention [3,[6][7...

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Section: Molecular Biology and Genetics Of Mitral Valve Prolapsementioning

confidence: 99%

Section: Molecular Biology and Genetics Of Mitral Valve Prolapsementioning

confidence: 99%

Section: Diagnosis Of Mitral Valve Prolapsementioning

confidence: 99%

Section: Prevalence Of Mitral Valve Prolapsementioning

confidence: 99%

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confidence: 99%

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Mitral Valve Prolapse: Current Views and Challenges (Review)

Клеменов¹

2017

Sovrem Tehnol Med

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Computational comparison of regional stress and deformation characteristics in tricuspid and bicuspid aortic valve leaflets

Cao

Sucosky

2016

Numer Methods Biomed Eng

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The bicuspid aortic valve (BAV) is the most common congenital valvular defect and a major risk factor for secondary calcific aortic valve disease. While hemodynamics is presumed to be a potential contributor to this complication, the validation of this theory has been hampered by the limited knowledge of the mechanical stress abnormalities experienced by BAV leaflets and their dependence on the heterogeneous BAV fusion patterns. The objective of this study was to compare computationally the regional and temporal fluid wall shear stress (WSS) and structural deformation characteristics in tricuspid aortic valve (TAV), type-0, and type-I BAV leaflets. Arbitrary Lagrangian-Eulerian fluid-structure interaction models were designed to simulate the flow and leaflet dynamics in idealized TAV, type-0, and type-I BAV geometries subjected to physiologic transvalvular pressure. The regional leaflet mechanics was quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI), temporal shear gradient (TSG), and stretch. The simulations identified regions of WSS overloads and increased WSS bidirectionality (174% increase in temporal shear magnitude, 0.10 increase in OSI on type-0 leaflets) in BAV leaflets relative to TAV leaflets. BAV leaflets also experienced larger radial deformations than TAV leaflets (4% increase in type-0 BAV leaflets). Type-I BAV leaflets exhibited contrasted WSS environments marked by WSS overloads on the non-coronary leaflet and sub-physiologic WSS levels on the fused leaflet. This study provides important insights into the mechanical characteristics of BAV leaflets, which may further our understanding of the role played by hemodynamic forces in BAV disease. Copyright © 2016 John Wiley & Sons, Ltd.

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Unravelling the proteome of degenerative human mitral valves

et al. 2015

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Degenerative mitral valve disease (DMVD), which includes the syndromes of mitral valve prolapse (MVP) and flail leaflet, is a common valvular condition which can be complicated by mitral regurgitation and adverse cardiovascular outcomes. Although several genetic and other studies of MVP in dog models have provided some information regarding the underlying disease mechanisms, the proteins and molecular events mediating human MVP pathogenesis have not been unraveled. In this study, we report the first large-scale proteome profiling of mitral valve tissue resected from patients with MVP. A total of 1134 proteins were identified, some of which were validated using SWATH-MS and western blotting. GO annotation of these proteins confirmed the validity of this proteome database in various cardiovascular processes. Among the list of proteins, we found several structural and extracellular matrix proteins, such as asporin, biglycan, decorin, lumican, mimecan, prolargin, versican, and vinculin, that have putative roles in the pathophysiology of MVP. These proteins could also be involved in the cardiac remodeling associated with mitral regurgitation. All MS data have been deposited in the ProteomeXchange with identifier PXD000774 (http://proteomecentral.proteomexchange.org/dataset/PXD000774).

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Genetic Basis of Familial Valvular Heart Disease

Cited by 42 publications

References 100 publications

Mitral Valve Prolapse: Current Views and Challenges (Review)

Mitral Valve Prolapse: Current Views and Challenges (Review)

Computational comparison of regional stress and deformation characteristics in tricuspid and bicuspid aortic valve leaflets

Unravelling the proteome of degenerative human mitral valves

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