| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), which belong to mitogen-activated protein kinases (MAPK), play a key role in the regulation of cell growth or apoptosis, or various gene expressions. In spite of the critical importance of MAPK for cell function in vitro, the role of MAPK in the pathophysiology of cardiovascular system in vivo is poorly understood. We have examined the activities of MAPK in various cardiovascular disease models. JNK 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. Cardiac increased JNK activitiy is associated with the development of cardiac hypertrophy, suggesting the role of JNK in cardiac hypertrophy. In chronic hypertensive rats, vascular ERK and JNK activities are continuously increased compared with normotensive rats, with the development of vascular thickening. Furthermore, balloon injury rapidly and transiently activates vascular ERK and JNK, followed by the activation of AP-1. This activation of ERK and JNK in injured artery is in part blocked by AT1 receptor antagonist, indicating the contribution of AT1 receptor in ERK and JNK activation in injured artery. In vivo gene transfer of dominant interfering mutants of ERK or JNK prevents vascular neointima formation after balloon injury. Thus, the enhanced activation of JNK or ERK occurs in various cardiovascular disease models, supporting the notion that MAPK may be important for cardiovascular hypertrophy and remodeling.
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