Avogaro Angelo, Fadini Gian Paolo, Gallo Alessandra, Pagnin Elisa, de Kreutzenberg Saula
Department of Clinical and Experimental Medicine, Division of Metabolic Diseases, University of Padova, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy.
Nutr Metab Cardiovasc Dis. 2006 Mar;16 Suppl 1:S39-45. doi: 10.1016/j.numecd.2005.10.015. Epub 2006 Feb 8.
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.
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.
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.
血管内皮细胞在维持健康状态下的心血管稳态中起主要作用。糖尿病（DM）严重损害内皮的舒张特性并导致内皮功能障碍，因此可将其视为心血管疾病进展的第一步。本研究的目的是阐明糖尿病中内皮功能障碍的可能机制。
我们已经表明，糖尿病患者循环淋巴细胞中NADPH氧化酶基因表达增加，并且这种基因表达的增加取决于代谢控制。高血糖可通过蛋白激酶C的激活介导其不良影响。我们已经表明糖尿病患者单核细胞膜相关PKCβ2活性增加。在血糖正常的情况下，这种活性降低了40%。最后，我们发现循环内皮祖细胞减少，循环内皮祖细胞是骨髓来源的内皮定向干细胞的一个亚群，可分化为成熟内皮细胞。
内皮功能障碍是动脉粥样硬化过程的初始步骤，是可逆的。因此，应做出重大努力，不仅要控制高血糖，还要控制心血管疾病的其他危险因素，以防止所有这些最终导致糖尿病患者过早死亡的过程的发生。
