Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100, Pisa, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Curr Hypertens Rep. 2019 Apr 4;21(4):32. doi: 10.1007/s11906-019-0930-2.
To examine the state of the art on the pathogenesis of endothelial dysfunction in the microcirculation of patients with obesity, focusing on the complex relationship between the consolidated and the novel mechanisms involved in this alteration.
Human obesity is associated with vascular endothelial dysfunction, caused by a reduced nitric oxide availability secondary to an enhanced oxidative stress production. Pro-inflammatory cytokine generation, secreted by perivascular adipose tissue, is a major mechanism whereby obesity is associated with a reduced vascular NO availability. Vasculature also represents a source of low-grade inflammation and oxidative stress which contribute to endothelial dysfunction in obese patients. Recently, a direct influence of arginase on endothelial function by reducing nitric oxide availability was demonstrated in small vessels from patients with severe obesity. This effect is modulated by ageing and related to the high levels of vascular oxidative stress. Oxidative stress, inflammation, and enzymatic pathways are important players in the pathophysiology of obesity-related vascular disease. The identification of new therapeutic approaches able to interfere with these mechanisms will result in more effective prevention of the cardiovascular complications associated with obesity.
探讨肥胖患者微循环内皮功能障碍发病机制的最新进展，重点关注该改变中固有和新出现机制之间的复杂关系。
人类肥胖与血管内皮功能障碍有关，其原因是由于氧化应激产生增强导致一氧化氮生成减少。由血管周围脂肪组织分泌的促炎细胞因子是肥胖与血管一氧化氮生成减少相关的主要机制之一。血管也是低度炎症和氧化应激的来源，这些炎症和应激会导致肥胖患者的内皮功能障碍。最近，在严重肥胖患者的小血管中发现，精氨酸酶通过减少一氧化氮的生成直接影响内皮功能。这种作用可被衰老调节，并与高水平的血管氧化应激有关。氧化应激、炎症和酶促途径是肥胖相关血管疾病病理生理学中的重要因素。确定能够干预这些机制的新治疗方法将有助于更有效地预防与肥胖相关的心血管并发症。
