Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress.

Abstract:

:Biomechanical stress is a major stimulus for cardiac hypertrophy and the transition to heart failure. By generating mice that harbor a ventricular restricted knockout of the gp130 cytokine receptor via Cre-IoxP-mediated recombination, we demonstrate a critical role for a gp130-dependent myocyte survival pathway in the transition to heart failure. Such conditional mutant mice have normal cardiac structure and function, but during aortic pressure overload, these mice display rapid onset of dilated cardiomyopathy and massive induction of myocyte apoptosis versus the control mice that exhibit compensatory hypertrophy. Thus, cardiac myocyte apoptosis is a critical point in the transition between compensatory cardiac hypertrophy and heart failure. gp130-dependent cytokines may represent a novel therapeutic strategy for preventing in vivo heart failure.

journal_name

Cell

journal_title

Cell

authors

Hirota H,Chen J,Betz UA,Rajewsky K,Gu Y,Ross J Jr,Müller W,Chien KR

doi

10.1016/s0092-8674(00)80729-1

subject

Has Abstract

pub_date

1999-04-16 00:00:00

pages

189-98

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(00)80729-1

journal_volume

97

pub_type

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