A G inhibitor reduces intimal hyperplasia in aortocoronary saphenous vein grafts

T Objective: Approximately 50% of aortocoronary saphenous vein grafts are occluded 10 years after coronary revascularization surgery. Intimal hyperplasia, a critical component in saphenous vein graft failure, is defined by vascular smooth muscle cell proliferation, which is mediated in part by subunits of heterotrimeric G proteins (G ) and downstream effectors such as mitogen-activated protein kinases. A peptide consisting of the carboxyl-terminus of the -adrenergic receptor kinase ( ARKct) binds G , thereby inhibiting G signaling. Utilizing a recombinant adenovirus containing the coding sequence for the ARKct peptide (Ad ARKct), this study investigates whether treatment of the vein graft with Ad ARKct reduces intimal hyperplasia in a large animal model of aortocoronary saphenous vein graft intimal hyperplasia.