Absher P M, Schneider D J, Baldor L C, Russell J C, Sobel B E
University of Vermont College of Medicine, Department of Medicine, Burlington 05405, USA.
Atherosclerosis. 1999 Apr;143(2):245-51. doi: 10.1016/s0021-9150(98)00295-0.
Proliferation in vivo of vascular smooth muscle cells occurs early in the course of atherosclerosis. Cultured smooth muscle cells (SMCs) explanted from aortas of JCR:LA-cp corpulent rats known to exhibit metabolic derangements and insulin resistance typical of type II diabetes early in life and to develop atherosclerosis later in life exhibit increased proliferation compared with SMCs from lean, normal rats. Vascular smooth muscle proliferation in vitro was found to be positively and significantly correlated with plasma insulin levels in vivo. Proliferation of aortic SMCs from JCR:LA-cp cp/cp corpulent rats cultured in vitro exhibited increased proliferation in the presence of exogenous insulin. Exercise and diet, selected as interventions designed to ameliorate the insulin resistance and hyperinsulinemia in the JCR:LA-cp cp/cp rat, effectively lowered blood insulin levels and decreased subsequent proliferation in vitro of aortic SMCs explanted from these animals. The results indicate that assessment of proliferation of vascular smooth muscle cells ex vivo may provide insight into the presence and severity of atherogenicity in association with insulin resistance in diverse species under diverse circumstances. Accordingly, with appropriate controls, it may be possible to use SMC proliferation ex vivo as a marker of the extent to which an intervention such as administration of insulin sensitizers to experimental animals and human subjects results in a change in behavior of vessel wall elements potentially indicative of amelioration of atherogenicity and detectable as judged from reduced proliferative rates of the cells ex vivo when they have been harvested from vessels exposed to a milieu in which insulin resistance has been attenuated.
血管平滑肌细胞在体内的增殖在动脉粥样硬化病程早期就会发生。从JCR:LA-cp肥胖大鼠主动脉中分离培养的平滑肌细胞（SMC），这些大鼠在生命早期就表现出典型的II型糖尿病代谢紊乱和胰岛素抵抗，后期会发展为动脉粥样硬化，与瘦的正常大鼠的SMC相比，其增殖能力增强。体外实验发现，血管平滑肌细胞的增殖与体内血浆胰岛素水平呈正相关且具有显著相关性。在体外培养的JCR:LA-cp cp/cp肥胖大鼠的主动脉SMC，在添加外源性胰岛素的情况下增殖增加。运动和饮食被选作改善JCR:LA-cp cp/cp大鼠胰岛素抵抗和高胰岛素血症的干预措施，它们有效地降低了血液胰岛素水平，并减少了从这些动物体内分离的主动脉SMC随后在体外的增殖。结果表明，体外评估血管平滑肌细胞的增殖可能有助于了解在不同情况下、不同物种中与胰岛素抵抗相关的动脉粥样硬化发生情况及严重程度。因此，在适当的对照下，有可能将体外SMC增殖作为一种标志物，用于评估向实验动物和人类受试者施用胰岛素增敏剂等干预措施在多大程度上改变血管壁成分的行为，这种行为变化可能预示动脉粥样硬化得到改善，并且当从暴露于胰岛素抵抗已减弱的环境中的血管中采集细胞时，可通过体外细胞增殖率降低来检测这种改善情况。
