Winocour P D
Department of Pathology, McMaster University, Hamilton, ON, Canada.
Can J Physiol Pharmacol. 1994 Mar;72(3):295-303. doi: 10.1139/y94-045.
Diabetes is associated with increased risk for atherosclerosis and its thromboembolic complications. Theories about mechanisms of atherosclerosis in diabetes are similar to those in the nondiabetic population. Platelets contribute to atherosclerosis through effects on vessels by materials released from the platelets, which interact with injured or altered vessels. In diabetes, platelets could contribute to enhanced atherosclerosis through hypersensitivity to agonists at sites of vessel injury and increased release of materials from adherent platelets. Diabetic platelets are hypersensitive to agonists in vitro, and alterations in a number of mechanisms involved in platelet activation occur in these platelets, which could contribute to the hypersensitivity. These alterations include increased presence of glycoprotein receptors for agonists and adhesive proteins on the platelet surface, increased fibrinogen binding, decreased membrane fluidity, enhanced arachidonate pathway activation with increased thromboxane A2 formation, and increased phosphoinositide turnover leading to increased inositol trisphosphate production, Ca2+ mobilization, and protein phosphorylation. There is some evidence for increased platelet activity in vivo in diabetes, but it is unclear whether this reflects platelet hypersensitivity or increased platelet turnover on already diseased vessels. Studies in diabetic animals indicate greater interaction of platelets with injured vessels and incorporation into experimentally induced thrombi, but it is unclear if this reflects changes in platelets or other factors. These changes could be contributing to the enhanced atherosclerosis and its clinical complications in diabetic patients.
糖尿病与动脉粥样硬化及其血栓栓塞并发症的风险增加有关。关于糖尿病患者动脉粥样硬化机制的理论与非糖尿病人群相似。血小板通过其释放的物质作用于血管，与受损或改变的血管相互作用，从而促进动脉粥样硬化。在糖尿病中，血小板可能通过对血管损伤部位的激动剂超敏反应以及黏附血小板释放物质增加，导致动脉粥样硬化加剧。糖尿病患者的血小板在体外对激动剂超敏，并且这些血小板中参与血小板激活的多种机制发生改变，这可能导致了超敏反应。这些改变包括血小板表面激动剂糖蛋白受体和黏附蛋白的增加、纤维蛋白原结合增加、膜流动性降低、花生四烯酸途径激活增强以及血栓素A2形成增加，还有磷酸肌醇代谢增加导致肌醇三磷酸生成增加、钙离子动员和蛋白质磷酸化。有一些证据表明糖尿病患者体内血小板活性增加，但尚不清楚这是否反映了血小板超敏反应或已患病血管上血小板周转率的增加。对糖尿病动物的研究表明，血小板与受损血管的相互作用更强，并更多地掺入实验诱导的血栓中，但尚不清楚这是否反映了血小板的变化或其他因素。这些变化可能导致糖尿病患者动脉粥样硬化加剧及其临床并发症。
