Insulin, Thrombin, ERK1/2 Kinase and Vascular Smooth Muscle Cells Proliferation

Author(s): Esma R. Isenovic, Sanja Soskic, Andreja Trpkovic, Branislava Dobutovic, Milan Popovic, Zoran Gluvic, Biljana Putnikovic, Pierre Marche

Journal Name: Current Pharmaceutical Design

Volume 16 , Issue 35 , 2010

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Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMC proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Signal transduction pathways in eukaryotic cells integrate diverse extracellular signals, and regulate complex biological responses such as growth, differentiation and death. One group of proline-directed Ser/Thr protein kinases, the mitogen-activated protein kinases (MAPKs), plays a central role in these signalling pathways. Much attention has focused in recent years on subfamilies of MAPKs, the extracellular signal regulated kinases (ERKs). Here we overview the work on ERKs 1 to 2, emphasising when possible their biological activities in VSMC proliferation. It is clear from numerosus studies including our own, that ERK1/ERK2 pathway has an imoprtant role in VSMC proliferation induced by insulin (INS) and thrombin. Despite the physiological and pathophysiological importance of INS and thrombin, possible signal transduction pathways involved in INS and thrombin regulation of VSMCs proliferation remains poorly understood. Thus, this review examines recent findings in signalling mechanisms involved in INS and thrombin- triggered VSMCs proliferation with particular emphasis on ERK1/2 signalling pathways. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.

Keywords: INS, thrombin, ERK1/2, VSMC, proliferation, Akt, MAPK, PDGF, atherosclerosis, hypertension, postangioplasty, restenosis, CARDIAC HYPERTROPHY, RTK, RhoGEFs

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Article Details

Year: 2010
Page: [3895 - 3902]
Pages: 8
DOI: 10.2174/138161210794454987
Price: $65

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