Jpn. J. Pharmacol. 80 (2), 97-102 (1999)

-Current Perspective-
Activation of Mitogen-Activated Protein Kinases in Cardiovascular Hypertrophy and Remodeling

Shokei Kim and Hiroshi Iwao

Department of Pharmacology, Osaka City University Medical School, 1- 4- 3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

Abstract: Extracellular signal-regulated kinases (ERKs) and c-jun NH2-terminal kinases (JNKs), which belong to the family of mitogen-activated protein kinases (MAPKs), play a key role in the regulation of cell
growth or apoptosis or various gene expressions. In spite of the critical importance of MAPKs for cell
function in vitro, the role of MAPKs in the pathophysiology of the cardiovascular system in vivo is poorly
understood. Recently, we have examined the activities of MAPKs in various cardiovascular disease models.
JNKs activity is chronically enhanced in cardiac hypertrophy of hypertensive rats or angiotensin II-infused
rats, which is followed by the increase in activator protein-1 (AP-1) activity composed of c-Fos and c-Jun
proteins. In chronic hypertensive rats, vascular ERKs and JNKs activities are continuously increased compared
with normotensive rats, with the development of vascular thickening. Furthermore, balloon injury
rapidly and transiently activates vascular ERKs and JNKs, followed by the activation of AP-1. This activation of ERKs and JNKs in injured artery is in part mediated by angiotensin AT1 receptor. Thus, the enhanced activation of JNKs or ERKs occurs in various cardiovascular disease models, supporting the notion that MAPKs may be a useful target for treatment of cardiovascular hypertrophy and remodeling.

Keywords: Cardiovascular disease, Angiotensin II, Activator protein-1, Gene expression

Copyrightę The Japanese Pharmacological Society 1999

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