The retardation of vasculopathy induced by attenuation of insulin resistance in the corpulent JCR:LA-cp rat is reflected by decreased vascular smooth muscle cell proliferation in vivo
The retardation of vasculopathy induced by attenuation of insulin resistance in the corpulent JCR:LA-cp rat is reflected by decreased vascular smooth muscle cell proliferation in vivo
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DOI：
10.1016/s0021-9150(98)00295-0
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发表时间：
1999-04-01
期刊：
影响因子：
5.3
通讯作者：
Sobel, BE
中科院分区：
文献类型：
--
作者：
Absher, PM;Schneider, DJ;Sobel, BE
血管平滑肌细胞的体内增殖发生在动脉粥样硬化过程的早期。从JCR：LA-cp肥胖大鼠的腹主动脉中培养的平滑肌细胞（SMC）与来自瘦的正常大鼠的SMC相比，表现出增加的增殖，已知肥胖大鼠在生命早期表现出典型的II型糖尿病的代谢紊乱和胰岛素抵抗，并在生命后期发展为动脉粥样硬化。体外血管平滑肌增殖与体内血浆胰岛素水平呈正相关。体外培养的JCR：LA-cp cp/cp肥胖大鼠主动脉平滑肌细胞的增殖在外源性胰岛素存在下表现出增殖增加。选择运动和饮食作为旨在改善JCR：LA-cp：cp大鼠胰岛素抵抗和高胰岛素血症的干预措施，有效地降低了血胰岛素水平，并减少了从这些动物中分离的主动脉SMC的体外增殖。结果表明，评估血管平滑肌细胞的增殖离体可能提供洞察的存在和严重程度的致动脉粥样硬化与胰岛素抵抗在不同的物种在不同的情况下。因此，通过适当的控制，可以使用离体SMC增殖作为干预程度的标记，所述干预例如向实验动物和人类受试者施用胰岛素敏化剂导致血管壁元件的行为变化，所述血管壁元件的行为变化潜在地指示动脉粥样硬化性的改善，并且当它们已经从血管壁中收获时，可以从离体细胞的增殖速率降低来判断，暴露于胰岛素抵抗已经减弱的环境中的血管。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
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. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.