342. Downregulation of Cardiomyocyte-Enriched Micrornas Contributes to Altered Gene Expression in Heart Failure

Dilated cardiomyopathy, a disease of unknown etiology and pathogenesis, is associated with heart failure and compensatory hypertrophy. Although cell and animal models suggest a role for altered gene expression in the transition to heart failure, there is a paucity of data derived from the study of human heart tissue. In this study, we used DNA microarray profiling to investigate changes in the expression of genes involved in apoptosis that occur in human idiopathic dilated cardiomyopathic hearts that had progressed to heart failure. We observed altered gene expression consistent with a proapoptotic shift in the TNF-α signaling pathway. Specifically, we found decreased expression of TNF-α- and NF-κB-induced antiapoptotic genes such as growth arrest and DNA damage-inducible ( GADD) 45β, Flice inhibitory protein ( FLIP), and TNF-induced protein 3 ( A20). Consistent with a role for apoptosis in heart failure, we also observed a significant decrease in phosphorylation of BAD at Ser-112. This study identifies several pathways that are altered in human heart failure and provides new targets for therapy.

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Aspects of Altered Gene Expression in Heart Failure and Myocardial Hypertrophy

Chronic Heart Failure ◽

10.1007/978-3-642-85913-7_14 ◽

1998 ◽

pp. 249-260

Author(s):

Michael Böhm ◽

Erland Erdmann

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Myocardial Hypertrophy ◽

Altered Gene Expression ◽

Altered Gene

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Altered gene expression profile in skeletal muscle after development of chronic heart failure

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(02)80879-8 ◽

2002 ◽

Vol 39 ◽

pp. 198

Author(s):

Nicolle Krankel ◽

Volker Adams ◽

Stephan Gielen ◽

Rainer Hambrecht ◽

Gerhard Schuler

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Skeletal Muscle ◽

Chronic Heart Failure ◽

Gene Expression Profile ◽

Expression Profile ◽

Altered Gene Expression ◽

Altered Gene

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Molecular and Microscopic Analysis of Altered Gene Expression in Transgenic and Gene Targeted Mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162521 ◽

1996 ◽

Vol 54 ◽

pp. 12-13

Author(s):

W. K. Jones ◽

J. Robbins

Keyword(s):

Gene Expression ◽

Pulmonary Veins ◽

Microscopic Analysis ◽

Mouse Tissue ◽

Adult Heart ◽

Heavy Chains ◽

Altered Gene Expression ◽

Altered Gene ◽

Pulmonary Myocardium

Two myosin heavy chains (MyHC) are expressed in the mammalian heart and are differentially regulated during development. In the mouse, the α-MyHC is expressed constitutively in the atrium. At birth, the β-MyHC is downregulated and replaced by the α-MyHC, which is the sole cardiac MyHC isoform in the adult heart. We have employed transgenic and gene-targeting methodologies to study the regulation of cardiac MyHC gene expression and the functional and developmental consequences of altered α-MyHC expression in the mouse.We previously characterized an α-MyHC promoter capable of driving tissue-specific and developmentally correct expression of a CAT (chloramphenicol acetyltransferase) marker in the mouse. Tissue surveys detected a small amount of CAT activity in the lung (Fig. 1a). The results of in situ hybridization analyses indicated that the pattern of CAT transcript in the adult heart (Fig. 1b, top panel) is the same as that of α-MyHC (Fig. 1b, lower panel). The α-MyHC gene is expressed in a layer of cardiac muscle (pulmonary myocardium) associated with the pulmonary veins (Fig. 1c). These studies extend our understanding of α-MyHC expression and delimit a third cardiac compartment.

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