Activation of mitogen-activated protein kinases in cardiovascular hypertrophy and remodeling.
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.
Kim
S
S
Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
Iwao
H
H
D000818:Animals; D001158:Arteries / Q000201:enzymology / Q000293:injuries; D006332:Cardiomegaly / Q000201:enzymology*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism
D011945:Receptors, Angiotensin; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases