In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 109, No. 16 ( 2004-04-27), p. 1938-1941
Abstract:
Background— Myocardial infarction causes a rapid and largely irreversible loss of cardiac myocytes that can lead to sudden death, ventricular dilation, and heart failure. Members of the mitogen-activated protein kinase (MAPK) signaling cascade have been implicated as important effectors of cardiac myocyte cell death in response to diverse stimuli, including ischemia-reperfusion injury. Specifically, activation of the extracellular signal–regulated kinases 1/2 (ERK1/2) has been associated with cardioprotection, likely through antagonism of apoptotic regulatory pathways. Methods and Results— To establish a causal relationship between ERK1/2 signaling and cardioprotection, we analyzed Erk1 nullizygous gene-targeted mice, Erk2 heterozygous gene-targeted mice, and transgenic mice with activated MEK1-ERK1/2 signaling in the heart. Although MEK1 transgenic mice were largely resistant to ischemia-reperfusion injury, Erk2 +/− gene-targeted mice showed enhanced infarction areas, DNA laddering, and terminal deoxynucleotidyl transferase–mediated dUTP biotin nick-end labeling (TUNEL) compared with littermate controls. In contrast, enhanced MEK1-ERK1/2 signaling protected hearts from DNA laddering, TUNEL, and preserved hemodynamic function assessed by pressure-volume loop recordings after ischemia-reperfusion injury. Conclusions— These data are the first to demonstrate that ERK2 signaling is required to protect the myocardium from ischemia-reperfusion injury in vivo.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.0000127126.73759.23
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2004
detail.hit.zdb_id:
1466401-X
Permalink