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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1037.)
© 2007 American Heart Association, Inc.

Vascular Biology

Smooth Muscle–Targeted Knockout of Connexin43 Enhances Neointimal Formation in Response to Vascular Injury

Yongbo Liao; Christopher P. Regan; Ichiro Manabe; Gary K. Owens; Kathy H. Day; Dave N. Damon; Brian R. Duling

From the Department of Anesthesiology (Y.L.), Department of Molecular Physiology and Biological Physics (G.K.O., D.N.D., B.R.D.), and Cardiovascular Research Center (K.H.D.), University of Virginia, Charlottesville, Va; Department of Pharmacology (C.P.R.), Merck Research Laboratories, West Point, Pa; Department of Cardiology (I.M.), University of Tokyo, Tokyo, Japan.

Correspondence to Dr Brian R. Duling, Department of Molecular Physiology and Biological Physics, University of Virginia, School of Medicine, MR-4 Building, Room 6051, Charlottesville, VA 22908. E-mail brd{at}virginia.edu

Objective— Vascular disease alters and reduces connexin expression and a reduction in connexin 43 (Cx43) expression diminishes the extent of atherosclerosis observed in a high-cholesterol diet murine model. We hypothesized that connexins might play a role in the smooth muscle cell response to vascular injury.

Methods and Results— We therefore studied a line of smooth muscle cell-specific, Cx43 gene knockout mice (SM Cx43 KO) in which the carotid arteries were injured, either by vascular occlusion or by a wire injury. In the SM Cx43 KO mice both types of injury manifested accelerated growth of the neointima and of the adventitia. Isolated vascular smooth muscle cells from the SM Cx43 KO mice grew at a slightly faster rate in culture, and to marginally higher saturation densities than those of control mice, but these changes were not adequate to explain the large changes in the injured vessels.

Conclusions— These observations provide direct evidence that smooth muscle Cx43 gap junctions play a multi-faceted role in modulating the in vivo growth response of vascular smooth muscle cells to vascular injury.

Injury to carotid arteries in which Cx43 had been deleted from the vascular smooth muscle produced markedly greater neointimal and adventitial growth than seen in control animals. Thus, smooth muscle Cx43 gap junctions may play a key role in modulating the growth response of vascular smooth muscle cells to vascular injury.

Key Words: adventitia • atherosclerosis • smooth muscle • thrombus

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