Liao Yongbo, Regan Christopher P, Manabe Ichiro, Owens Gary K, Day Kathy H, Damon Dave N, Duling Brian R
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA.
Arterioscler Thromb Vasc Biol. 2007 May;27(5):1037-42. doi: 10.1161/ATVBAHA.106.137182. Epub 2007 Mar 1.
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.
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.
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.
血管疾病会改变并降低连接蛋白的表达，而连接蛋白43（Cx43）表达的降低会减轻高胆固醇饮食小鼠模型中动脉粥样硬化的程度。我们推测连接蛋白可能在平滑肌细胞对血管损伤的反应中发挥作用。
因此，我们研究了平滑肌细胞特异性Cx43基因敲除小鼠（SM Cx43 KO）品系，通过血管闭塞或钢丝损伤对其颈动脉进行损伤。在SM Cx43 KO小鼠中，这两种损伤均表现为内膜和外膜加速生长。从SM Cx43 KO小鼠分离出的血管平滑肌细胞在培养中生长速度略快，饱和密度略高于对照小鼠，但这些变化不足以解释受损血管中的巨大变化。
这些观察结果提供了直接证据，表明平滑肌Cx43间隙连接在调节血管平滑肌细胞对血管损伤的体内生长反应中发挥多方面作用。
