Current Hypertension Reviews

Prof. Kazuomi Kario
Jichi Medical University
School of Medicine
Tochigi
Japan

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Role of ERK1/2 Activation In Thrombin-Induced Vascular Smooth Muscle Cell Hypertrophy

Author(s): Esma R. Isenovic, Andreja Trpkovic, Zorica Zakula, Goran Koricanac, Pierre Marche.

Abstract:

It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. It is generally considered that the phosphorylation/dephosphorylation reactions of a variety of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including thrombin. ERK1/2 activation by G-protein-coupled receptors (GPCRs) has been shown to be Ca2+-dependent and to require the transactivation of epidermal growth factor receptor (EGFR). In addition, it is generally admitted that variations of the intracellular Ca2+ concentration ([Ca2+] i) play an important role in the transduction of mitogenic signal. Recently, we have shown that in thrombin-stimulated VSMCs, EGFR-independent activation of ERK1/2 activation could occur when agonist-induced ([Ca2+] i) elevation was reduced. This review examines recent findings in ERK1/2 signaling pathway that have been identified as critically important mediator of VSMCs hypertrophy and vascular diseases. 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: Vascular smooth muscle cells, hypertrophy, thrombin, epidermal growth factor receptor, receptor, ERK1/2 signaling pathway, calcium-channels

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Article Details

VOLUME: 4
ISSUE: 3
Year: 2008
Page: [190 - 196]
Pages: 7
DOI: 10.2174/157340208785132590
Price: $58