G beta gamma-mediated signaling: new therapeutic target for proliferative vascular disease

Abstract

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 G beta gamma-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 G beta gamma signaling in vivo has resulted in inhibition of intimal hyperplasia in experimental models of vein-graft failure and restenosis.