Stout R W
Department of Geriatric Medicine, Belfast.
Eur J Epidemiol. 1992 May;8 Suppl 1:134-5. doi: 10.1007/BF00145365.
A number of processes are involved in the pathogenesis of atherosclerosis. These include an "injury" to the endothelial cell barrier of the inner lining of the artery, infiltration of the artery by lipid filled monocyte-macrophages, proliferation of smooth muscle cells, synthesis of connective tissue and thrombus formation. Insulin may be involved in several of these processes. Over 40 years ago it was shown that insulin is necessary for the production of experimental atherosclerosis in cholesterol fed, alloxan diabetic rabbits. Insulin inhibits regression and stimulates formation of lipid containing lesions in a number of species, and can promote lesions in animals fed normal diets. Insulin is also related to lipid metabolism in the artery wall and interacts with blood pressure to stimulate lipid synthesis in arteries. Arterial smooth muscle cells cultured from a number of species including humans proliferate in response to levels of insulin similar to those found in normal human physiology. The proliferative effects of insulin are mediated by the insulin-like growth factor receptor and hence may not be impaired in states of insulin resistance. Insulin also stimulates arterial smooth muscle cell migration. Insulin stimulates cholesterol synthesis in cultured smooth muscle cells and enhances LDL receptor activity in a number of cell types. Insulin stimulates connective tissue synthesis, and promotes clotting.
动脉粥样硬化的发病机制涉及多个过程。这些过程包括动脉内膜内皮细胞屏障的“损伤”、脂质填充的单核细胞 - 巨噬细胞对动脉的浸润、平滑肌细胞增殖、结缔组织合成以及血栓形成。胰岛素可能参与其中的多个过程。40多年前就已表明，胰岛素对于在喂食胆固醇的四氧嘧啶糖尿病兔中产生实验性动脉粥样硬化是必需的。胰岛素在许多物种中抑制病变消退并刺激含脂质病变的形成，并且可以促进正常饮食喂养动物的病变。胰岛素还与动脉壁中的脂质代谢相关，并与血压相互作用以刺激动脉中的脂质合成。从包括人类在内的许多物种培养的动脉平滑肌细胞会对类似于正常人体生理状态下的胰岛素水平产生增殖反应。胰岛素的增殖作用由胰岛素样生长因子受体介导，因此在胰岛素抵抗状态下可能不会受损。胰岛素还刺激动脉平滑肌细胞迁移。胰岛素刺激培养的平滑肌细胞中的胆固醇合成，并增强多种细胞类型中的低密度脂蛋白受体活性。胰岛素刺激结缔组织合成，并促进凝血。
