Signaling pathways for cardiac hypertrophy and failure.

Heart failure is a leading cause of mortality in the United States. As a result of advances in genetic technology, a molecular basis of heart failure is emerging.1,2 This review highlights the ways in which these insights are leading to new therapeutic targets in patients with acquired forms of heart failure. Morphologic Classification of Cardiac Hypertrophy Myocardial hypertrophy is an early milestone during the clinical course of heart failure and an important risk factor for subsequent cardiac morbidity and mortality. In response to a variety of mechanical, hemodynamic, hormonal, and pathologic stimuli, the heart adapts to increased demands for . . .

[1]  J Ross,et al.  Cardiac Muscle Cell Hypertrophy and Apoptosis Induced by Distinct Members of the p38 Mitogen-activated Protein Kinase Family* , 1998, The Journal of Biological Chemistry.

[2]  Jiahuai Han,et al.  Cardiac Hypertrophy Induced by Mitogen-activated Protein Kinase Kinase 7, a Specific Activator for c-Jun NH2-terminal Kinase in Ventricular Muscle Cells* , 1998, The Journal of Biological Chemistry.

[3]  K. Chien,et al.  Genes and physiology: molecular physiology in genetically engineered animals. , 1996, The Journal of clinical investigation.

[4]  Minoru Hongo,et al.  MLP-Deficient Mice Exhibit a Disruption of Cardiac Cytoarchitectural Organization, Dilated Cardiomyopathy, and Heart Failure , 1997, Cell.

[5]  J Ross,et al.  Molecular and physiological alterations in murine ventricular dysfunction. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. Chien,et al.  Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  K. Chien,et al.  Complexity in simplicity: monogenic disorders and complex cardiomyopathies. , 1999, The Journal of clinical investigation.

[8]  Frederick J. Schoen,et al.  A Mouse Model of Familial Hypertrophic Cardiomyopathy , 1996, Science.

[9]  K. Chien,et al.  Stress Pathways and Heart Failure , 1999, Cell.

[10]  J. Ross,et al.  Loss of a gp130 Cardiac Muscle Cell Survival Pathway Is a Critical Event in the Onset of Heart Failure during Biomechanical Stress , 1999, Cell.

[11]  R. Lefkowitz,et al.  Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Heath,et al.  Cardiotrophin-1 Activates a Distinct Form of Cardiac Muscle Cell Hypertrophy , 1996, The Journal of Biological Chemistry.

[13]  J. Sadoshima,et al.  Critical Role of the AT1 Receptor Subtype , 2005 .

[14]  K. Chien,et al.  Rho Is Required for Gαq and α1-Adrenergic Receptor Signaling in Cardiomyocytes , 1996, The Journal of Biological Chemistry.

[15]  M. C. Lin,et al.  Heart and lung disease in engineered mice , 1995, Nature Medicine.

[16]  A. Means,et al.  Targeted developmental overexpression of calmodulin induces proliferative and hypertrophic growth of cardiomyocytes in transgenic mice. , 1993, Endocrinology.

[17]  E. Lakatta,et al.  Coupling of beta2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes. , 1999, Circulation research.

[18]  S. Vatner,et al.  Adverse Effects of Chronic Endogenous Sympathetic Drive Induced by Cardiac Gsα Overexpression , 1996 .

[19]  H. Nishi,et al.  Expression of proto-oncogenes and gene mutation of sarcomeric proteins in patients with hypertrophic cardiomyopathy. , 1998, Circulation research.

[20]  E. Neer,et al.  Transient cardiac expression of constitutively active Galphaq leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  G. Dorn,et al.  Cardiac-specific overexpression of phospholamban alters calcium kinetics and resultant cardiomyocyte mechanics in transgenic mice. , 1996, The Journal of clinical investigation.

[22]  S. Powers,et al.  HRas-dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy. , 1993, The Journal of biological chemistry.

[23]  John W. Adams,et al.  Enhanced Galphaq signaling: a common pathway mediates cardiac hypertrophy and apoptotic heart failure. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  T. Yamazaki,et al.  Specific Interaction of Topoisomerase II and the CD3 Chain of the T Cell Receptor Complex (*) , 1996, The Journal of Biological Chemistry.

[25]  K. Chien,et al.  Transcriptional regulation during cardiac growth and development. , 1993, Annual review of physiology.

[26]  D. Absher,et al.  Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following alpha 1-adrenergic stimulation. , 1994, The Journal of biological chemistry.

[27]  Y. Hayashizaki,et al.  Identification of the Syrian hamster cardiomyopathy gene. , 1997, Human Molecular Genetics.

[28]  R. Lefkowitz,et al.  Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy. , 1998, Science.

[29]  K. Chien,et al.  Targeting gene expression to specific cardiovascular cell types in transgenic mice. , 1993, Hypertension.

[30]  J Ross,et al.  Ras-dependent pathways induce obstructive hypertrophy in echo-selected transgenic mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Sadoshima,et al.  The heterotrimeric G q protein‐coupled angiotensin II receptor activates p21 ras via the tyrosine kinase‐Shc‐Grb2‐Sos pathway in cardiac myocytes. , 1996, The EMBO journal.

[32]  R. Lefkowitz,et al.  Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor. , 1994, Science.

[33]  R Aikawa,et al.  Endothelin-1 Is Involved in Mechanical Stress-induced Cardiomyocyte Hypertrophy (*) , 1996, The Journal of Biological Chemistry.

[34]  Jeffrey Robbins,et al.  A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy , 1998, Cell.

[35]  G. Dorn,et al.  Transgenic Gαq overexpression induces cardiac contractile failure in mice , 1997 .

[36]  K. Chien,et al.  Ventricular Expression of a MLC-2v-ras Fusion Gene Induces Cardiac Hypertrophy and Selective Diastolic Dysfunction in Transgenic Mice (*) , 1995, The Journal of Biological Chemistry.

[37]  K. Chien,et al.  Physiological assessment of complex cardiac phenotypes in genetically engineered mice. , 1997, The American journal of physiology.

[38]  J. Ross,et al.  Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[39]  R. Lefkowitz,et al.  Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. , 1995, Science.

[40]  K. Chien,et al.  Cardiotrophin 1 (CT-1) Inhibition of Cardiac Myocyte Apoptosis via a Mitogen-activated Protein Kinase-dependent Pathway , 1997, The Journal of Biological Chemistry.

[41]  Michael E. Greenberg,et al.  Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis , 1995, Science.

[42]  M. Shichiri,et al.  Insulinlike Growth Factor‐I Induces Hypertrophy With Enhanced Expression of Muscle Specific Genes in Cultured Rat Cardiomyocytes , 1993, Circulation.

[43]  J. Ross,et al.  Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure. , 1995, The Journal of clinical investigation.

[44]  M. Lohse,et al.  Progressive hypertrophy and heart failure in beta1-adrenergic receptor transgenic mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[45]  K. Chien,et al.  Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy. , 1990, The Journal of biological chemistry.

[46]  T. Doetschman,et al.  Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation. , 1994, Circulation research.

[47]  K. Chien,et al.  Ventricular muscle-restricted targeting of the RXRalpha gene reveals a non-cell-autonomous requirement in cardiac chamber morphogenesis. , 1998, Development.

[48]  J. Ross,et al.  Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy , 1991, Proceedings of the National Academy of Sciences of the United States of America.