Endothelial dysfunction in type 2 diabetes mellitus.
OBJECTIVE
Vascular endothelial cells play a major role in maintaining cardiovascular homeostasis in health. Diabetes mellitus (DM) substantially impairs the vasodilating properties of the endothelium and leads to endothelial dysfunction, which can thus be considered the first step in the progression of cardiovascular disease. The aim of the present study is to illustrate possible mechanisms responsible for endothelial dysfunction in DM.


RESULTS
We have shown that NADPH oxidase gene expression is increased in circulating lymphomonocytes from patients with DM, and that this increased gene expression is dependent upon metabolic control. Hyperglycemia can mediate its adverse effects through the activation of protein kinase C. We have shown an increase in membrane-associated PKC beta 2 activity in monocytes from patients with DM. This activity was reduced by 40% in the euglycemic condition. Finally, we show a reduction of the circulating endothelial progenitor cells, a subset of bone marrow-derived endothelial-oriented stem cells, which can give rise to mature endothelial cells.


CONCLUSIONS
Endothelial dysfunction, the initial step of the atherosclerotic process, is reversible. Thus, major efforts should be made to control not only hyperglycemia but also the other risk factors for cardiovascular disease, in order to prevent the onset of all these processes that eventually leads the diabetic patient to premature death.
Avogaro
Angelo
A
Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padova, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy. angelo.avogaro@unipd.it
Fadini
Gian Paolo
GP
Gallo
Alessandra
A
Pagnin
Elisa
E
de Kreutzenberg
Saula
S
D048909:Diabetes Complications; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism
D009569:Nitric Oxide; D019255:NADPH Oxidases; D011493:Protein Kinase C