Coordinatore del progetto “Insulin Resistance and Coronary Disease: insights into inflammation, thrombosis and metabolic sindrome”

Type 2 diabetes and its antecedents, including impaired glucose tolerance and syndromes of insulin resistance, are powerful risk factors for premature and accelerated cardiovascular disease. Mortality attributable to coronary artery disease is 4.3-fold higher in patients with diabetes compared with that in nondiabetic subjects. Of importance is the fact that heart disease patients with diabetes have a higher incidence of mortality during and following an acute myocardial infarction and a high risk for progression to heart failure post-infarction. Altered coagulation and platelet function, impaired fibrinolysis, decreased HDL- and elevated LDL-cholesterol, high triglycerides, increased VLDL, nephropathy, hypertension, obesity are all conditions that may be implicated in this poor outcome. In addition studies on obesity and insulin resistance in humans have revealed a clear association between activation of pro-inflammatory signaling pathways and decreased peripheral insulin sensitivity. In this context "the high mobility group (HMGB)-1" has been shown to function as a critical mediator in inflammatory diseases being secreted by endothelial, smooth muscle vascular and monocyte/macrophage cells. Finally, type 2 diabetes patients present a paradoxically deficits in bone strength, but no information is available on the role of insulin and fetuin A in vascular calcification in diabetic patients with acute or stable coronary syndrome. The project will provide insights into the thrombotic phenotype/propensity of diabetic patients with stable angina specifically evaluating the platelet-, platelet-leukocyte complexes-, and microparticle-associated TF expression compared to non-diabetic stable angina patients. Evaluation of the genomic and proteomic profile of platelets and/or plasma from diabetic patients with stable angina compared to non-diabetic stable angina patients will also be performed. Further, the project will establish the relationships (if any) between insulin level, fetuin A and apoB48-containing TGRL in diabetic patients with stable angina complicated by vascular calcification. It will also draw the role of diabetic ppTGRL on macrophage athero-related functions and it will assess how these alterations are modulated by clinical therapies. Finally, the role of HMGB-1 in diabetic and atherosclerotic process will be investigated.