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Gbetagamma‐Mediated Signaling: New Therapeutic Target for Proliferative Vascular Disease
Author(s) -
Iaccarino Guido,
Koch Walter J.
Publication year - 1999
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/713803509
Subject(s) - restenosis , intimal hyperplasia , signal transduction , microbiology and biotechnology , vascular smooth muscle , extracellular , biology , receptor , pharmacology , cancer research , medicine , endocrinology , smooth muscle , stent
Proliferation of vascular smooth muscle (VSM) severely affects the outcome of coronary artery bypass and angioplasty procedures, causing the failure of venous grafts or restenosis of the reopened vessel. Investigation into the mechanisms underlying the process of VSM cellular proliferation has provided evidence that intracellular signaling mechanisms triggered by extracellular hormonal factors acting through G protein‐coupled receptors, can mediate and sustain this pathological process. Inhibition of common pathways of G protein‐coupled receptor signaling has recently proven effective in preventing VSM cellular activation and proliferation. In particular, inhibition of the Gbetagamma‐mediated mitogen‐activated protein (MAP) kinase signaling pathway results in the inhibition of VSM proliferation in vitro. Moreover, use of adenoviral vectors to deliver a peptide inhibitor of Gbetagamma signaling in vivo has resulted in inhibition of intimal hyperplasia in experimental models of vein‐graft failure and restenosis.