Institutes

Cardiodiabetes and core Lab

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Group Leader

Lucilla Monti

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Research activity is focused on type 2 diabetes mellitus and cardiovascular diseases. Diabetic patients have an increased incidence of coronary disease and myocardial infarction compared with non-diabetic patients with a similar risk profile. Type 2 diabetes and cardiovascular diseases could be considered different aspects of the same syndrome: i.e. the metabolic syndrome. Metabolic syndrome is a cluster of metabolic abnormalities which includes obesity, insulin resistance, dyslipidemia, hypertension, endothelial dysfunction. Endothelial dysfunction, which represents a common trait of the type 2 diabetes and cardiovascular diseases, is characterized by a reduction of the bioavailability of vasodilators, mainly nitric oxide, which causes an impairment of endothelium-dependent vasodilation. Endothelium-derived nitric oxide is a potent endogenous vasodilator that plays a major role in vascular tone; it is synthesized by endothelial nitric oxide synthase in a multistep reaction from L-arginine. Genetic variants on eNOS gene are associated to type 2 diabetes, cardiovascular diseases and metabolic syndrome.

The group recently demonstrated that these variants produce alternative splicing causing the generation of a novel isoform of eNOS protein, truncated in the C-terminal region and with an altered function. In particular, a significant decrease of insulin sensitivity and endothelial progenitor cells (EPCs), and an increase in proatherogenic markers (ADMA) have been found in subjects carrying this alternative splicing.