The genetic basis for cardiac remodeling

被引:226
作者
Ahmad, F [1 ]
Seidman, JG
Seidman, CE
机构
[1] Univ Pittsburgh, Sch Med, Cardiovasc Inst, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA
[3] Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA 15213 USA
[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[5] Howard Hughes Med Inst, Boston, MA 02115 USA
关键词
hypertrophic cardiomyopathy; dilated cardiomyopathy; restrictive cardiomyopathy; arrhythmogenic right ventricular dysplasia/cardiomyopathy; PRKAG2; cardiomyopathy;
D O I
10.1146/annurev.genom.6.080604.162132
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Cardiomyopathies are primary disorders of cardiac muscle associated with abnormalities of cardiac wall thickness, chamber size, contraction, relaxation, conduction, and rhythm. They are a major cause of morbidity and mortality at all ages and, like acquired forms of cardiovascular disease, often result in heart failure. Over the past two decades, molecular genetic studies of humans and analyses of model organisms have made remarkable progress in defining the pathogenesis of cardiomyopathies. Hypertrophic cardiomyopathy can result from mutations in 11 genes that encode sarcomere proteins, and dilated cardiomyopathy is caused by mutations at 25 chromosome loci where genes encoding contractile, cytoskeletal, and calcium regulatory proteins have been identified. Causes of cardiornyopathies associated with clinically important cardiac arrhythmias have also been discovered: Mutations in cardiac metabolic genes cause hypertrophy in association with ventricular pre-excitation and mutations causing arrhythmogenic right ventricular dysplasia were recently discovered in protein constituents of desmosomes. This considerable genetic heterogeneity suggests that there are multiple pathways that lead to changes in heart structure and function. Defects in myocyte force generation, force transmission, and calcium homeostasis have emerged as particularly critical signals driving these pathologies. Delineation of the cell and molecular events triggered by cardiomyopathy gene mutations provide new fundamental knowledge about myocyte biology and organ physiology that accounts for cardiac remodeling and defines mechanistic pathways that lead to heart failure.
引用
收藏
页码:185 / 216
页数:36
相关论文
共 191 条
[1]   Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23 [J].
Ahmad, F ;
Li, DX ;
Karibe, A ;
Gonzalez, O ;
Tapscott, T ;
Hill, R ;
Weilbaecher, D ;
Blackie, P ;
Furey, M ;
Gardner, M ;
Bachinski, LL ;
Roberts, R .
CIRCULATION, 1998, 98 (25) :2791-2795
[2]   Glycogen storage diseases presenting as hypertrophic cardiomyopathy [J].
Arad, M ;
Maron, BJ ;
Gorham, JM ;
Johnson, WH ;
Saul, JP ;
Perez-Atayde, AR ;
Spirito, P ;
Wright, GB ;
Kanter, RJ ;
Seidman, CE ;
Seidman, JG .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (04) :362-372
[3]   Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy [J].
Arad, M ;
Moskowitz, IP ;
Patel, VV ;
Ahmad, F ;
Perez-Atayde, AR ;
Sawyer, DB ;
Walter, M ;
Li, GH ;
Burgon, PG ;
Maguire, CT ;
Stapleton, D ;
Schmitt, JP ;
Guo, XX ;
Pizard, A ;
Kupershmidt, S ;
Roden, DM ;
Berul, CI ;
Seidman, CE ;
Seidman, JG .
CIRCULATION, 2003, 107 (22) :2850-2856
[4]   Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy [J].
Arad, M ;
Benson, DW ;
Perez-Atayde, AR ;
McKenna, WJ ;
Sparks, EA ;
Kanter, RJ ;
McGarry, K ;
Seidman, JG ;
Seidman, CE .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (03) :357-362
[5]   Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside [J].
Badorff, C ;
Knowlton, KU .
MEDICAL MICROBIOLOGY AND IMMUNOLOGY, 2004, 193 (2-3) :121-126
[6]   X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): An update [J].
Barth, PG ;
Valianpour, F ;
Bowen, VM ;
Lam, J ;
Duran, M ;
Vaz, FM ;
Wanders, RJA .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2004, 126A (04) :349-354
[7]  
Basso C, 1999, Cardiol Rev, V7, P127, DOI 10.1097/00045415-199905000-00009
[8]   Arrhythmogenic right ventricular cardiomyopathy - Dysplasia, dystrophy, or myocarditis? [J].
Basso, C ;
Thiene, G ;
Corrado, D ;
Angelini, A ;
Nava, A ;
Valente, M .
CIRCULATION, 1996, 94 (05) :983-991
[9]   Familial effort polymorphic ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy map to chromosome 1q42-43 [J].
Bauce, B ;
Nava, A ;
Rampazzo, A ;
Daliento, L ;
Muriago, M ;
Basso, C ;
Thiene, G ;
Danieli, GA .
AMERICAN JOURNAL OF CARDIOLOGY, 2000, 85 (05) :573-579
[10]   Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death early diagnosis of asymptomatic carriers - Early diagnosis of asymptomatic carriers [J].
Bauce, B ;
Rampazzo, A ;
Basso, C ;
Bagattin, A ;
Daliento, L ;
Tiso, N ;
Turrini, P ;
Thiene, G ;
Danieli, GA ;
Nava, A .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2002, 40 (02) :341-349