Policlinico A. Gemelli IRCCS, Roma, Italy.
Department of Internal Medicine, Università Tor Vergata, Roma, Italy.
Vascul Pharmacol. 2020 May-Jun;128-129:106676. doi: 10.1016/j.vph.2020.106676. Epub 2020 Mar 26.
Activation of fractalkine and other chemokines plays an important role in atherogenesis and, in conjunction with endothelial dysfunction, promotes premature vascular damage in obesity and diabetes. We hypothesized that increased circulating fractalkine coexists with impaired vasomotor function in metabolically healthy or unhealthy obesity, and that treatment with antidiabetic drugs may impact these abnormalities in type 2 diabetes. Compared to lean subjects, in both obese groups the vasodilator responses to acetylcholine and sodium nitroprusside were impaired (both P < .001); ET-receptor blockade resulted in greater vasodilation (both P < .001); and plasma levels of fractalkine, E-selectin and monocyte chemoattractant protein (MCP)-1 were increased (all P < .05). In diabetic patients, oral antidiabetic drugs (glyburide, metformin or pioglitazone) reduced circulating levels fractalkine and E-selectin (both P < .05), without affecting vascular responses (all P > .05). Our findings indicate that insulin resistant states are associated with elevated atherogenic chemokines and impaired vascular reactivity. Antidiabetic treatment results in lower circulating fractalkine, which may provide cardiovascular benefits.
fractalkine 和其他趋化因子的激活在动脉粥样硬化的形成中起着重要作用，并且与内皮功能障碍一起，促进肥胖和糖尿病患者的血管早期损伤。我们假设在代谢健康或不健康的肥胖中，循环 fractalkine 的增加与血管舒缩功能障碍并存，并且抗糖尿病药物的治疗可能会影响 2 型糖尿病患者的这些异常。与瘦人相比，在肥胖组中，乙酰胆碱和硝普钠引起的血管舒张反应均受损（均 P<.001）；内皮素受体阻断剂导致更大的血管舒张（均 P<.001）；循环 fractalkine、E-选择素和单核细胞趋化蛋白-1（MCP-1）水平升高（均 P<.05）。在糖尿病患者中，口服抗糖尿病药物（格列吡嗪、二甲双胍或吡格列酮）降低了循环 fractalkine 和 E-选择素的水平（均 P<.05），而不影响血管反应（均 P>.05）。我们的研究结果表明，胰岛素抵抗状态与升高的动脉粥样硬化趋化因子和血管反应性受损有关。抗糖尿病治疗可降低循环 fractalkine 水平，从而可能提供心血管获益。
