Murphy L J, Ghahary A, Chakrabarti S
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Diabetes. 1990 Jun;39(6):657-62. doi: 10.2337/diab.39.6.657.
Smooth muscle cell proliferation may be important in pathogenesis of atherosclerosis. Because insulinlike growth factor I (IGF-I) is a potent mitogen for arterial smooth muscle cells in culture, we examined the hypothesis that IGF-I functions as an autocrine growth factor in the aorta. We also investigated the role of insulin in regulation of IGF-I expression in the aorta. With immunohistochemical and in situ hybridization techniques, IGF-I immunoreactivity and IGF-I mRNA were localized to the smooth muscle layer of the aorta. In diabetic rats, aortic IGF-I mRNA abundance was significantly reduced to 60.3 +/- 2.9% of controls (P less than 0.01). In nondiabetic rats, administration of insulin as an acute bolus (10 U i.p.) or a chronic infusion (2.4 U/day for 5 days) resulted in an approximately twofold increase in abundance of IGF-I mRNA in the aorta. These observations are consistent with the hypothesis that IGF-I may function as an autocrine growth factor in the aorta and suggest that one of the mechanisms whereby hyperinsulinism may favor atherogenesis is enhanced expression of IGF-I in the vessel wall.
平滑肌细胞增殖在动脉粥样硬化发病机制中可能起重要作用。由于胰岛素样生长因子I（IGF-I）在体外培养中是动脉平滑肌细胞的一种强大促有丝分裂原，我们检验了IGF-I在主动脉中作为自分泌生长因子发挥作用的假说。我们还研究了胰岛素在调节主动脉中IGF-I表达方面的作用。运用免疫组织化学和原位杂交技术，IGF-I免疫反应性和IGF-I mRNA定位于主动脉的平滑肌层。在糖尿病大鼠中，主动脉IGF-I mRNA丰度显著降低至对照组的60.3±2.9%（P<0.01）。在非糖尿病大鼠中，静脉注射一次大剂量胰岛素（10 U腹腔注射）或持续输注胰岛素（2.4 U/天，共5天）导致主动脉中IGF-I mRNA丰度增加约两倍。这些观察结果与IGF-I可能在主动脉中作为自分泌生长因子发挥作用的假说一致，并提示高胰岛素血症可能促进动脉粥样硬化形成的机制之一是血管壁中IGF-I表达增强。
