Platelets, vascular disease, and diabetes mellitus.
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.
Winocour
P D
PD
Department of Pathology, McMaster University, Hamilton, ON, Canada.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D006801:Humans; D014652:Vascular Diseases / Q000097:blood* / Q000503:physiopathology