title: Endothelial dysfunction in diabetes mellitus.
abstract: Diabetes mellitus is associated with accelerated atherosclerosis and an increased prevalence of cardiovascular disease. Although the link between diabetes and cardiovascular disease is not fully understood, loss of the modulatory role of the endothelium could be implicated in the pathogenesis of diabetic vascular complications. There is substantial evidence that vasodilatation mediated by endothelium-derived nitric oxide (NO) is impaired in animal models of diabetes and in patients with insulin-dependent and non-insulin-dependent diabetes mellitus. NO is a principal factor involved in the antiatherosclerotic properties of the endothelium. NO interferes with key events in the development of atherosclerosis, such as vascular tone, monocyte and leukocyte adhesion to the endothelium, platelet-vessel wall interaction, and smooth muscle proliferation. Therefore, the pathogenesis of diabetic vascular disease may involve a reduced bioavailability of endothelium-derived NO. Although mechanisms by which diabetes contributes to endothelial dysfunction are currently unknown, it is likely that hyperglycemia, the hallmark of diabetes mellitus, may initiate this abnormality. Hyperglycemia-induced endothelial dysfunction may result from decreased production of NO, inactivation of NO by oxygen-derived free radicals, and/or increased production of endothelium-derived contracting factors, which oppose the protective activity of NO. This review summarizes evidence for endothelial dysfunction in diabetic patients and animals and the effects of prolonged exposure to elevated glucose in normal blood vessels and cultured endothelium. A better understanding of the mechanism(s) of hyperglycemia-induced endothelial dysfunction may unmask new preventive strategies to reduce cardiovascular morbidity and mortality in this condition.
authors.affiliation: Cardiology and Cardiovascular Research, Institute of Physiology, University Hospital, Zurich, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Cosentino
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans