Platelet activation in type 2 diabetes mellitus.
The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, pro-thrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population.
Department of Experimental Medicine & Pathology, University of Rome La Sapienza, Italy.
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P
Ferroni
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Basili
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Falco
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Davì
D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation; D008954:Models, Biological; D018384:Oxidative Stress; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D016718:Arachidonic Acid; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2