Endothelial-Vasoprotective Effects of High-Density Lipoprotein Are Impaired in Patients With Type 2 Diabetes Mellitus but Are Improved After Extended-Release Niacin Therapy
Endothelial-Vasoprotective Effects of High-Density Lipoprotein Are Impaired in Patients With Type 2 Diabetes Mellitus but Are Improved After Extended-Release Niacin Therapy
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DOI：
10.1161/circulationaha.108.836346
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发表时间：
2010-01-05
期刊：
影响因子：
37.8
通讯作者：
Landmesser, Ulf
中科院分区：
文献类型：
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作者：
Sorrentino, Sajoscha A.;Besler, Christian;Landmesser, Ulf
背景-高密度脂蛋白（HDL）升高疗法目前正在进行深入评估，但HDL的作用可能是高度异质性的。因此，我们比较了HDL对健康受试者和2型糖尿病患者的内皮细胞的影响，低HDL（符合代谢综合征的标准），他们经常被认为是HDL升高治疗。此外，在糖尿病患者中，我们研究了缓释（ER）烟酸治疗对HDL.Methods和Results-HDL的内皮效应的影响，HDL.Methods和Results-HDL从健康受试者（n = 10）和2型糖尿病患者（n = 33）通过连续ultracentravation分离。高密度脂蛋白对内皮细胞一氧化氮和超氧化物产生的影响，其特征在于通过电子自旋共振光谱分析。检测HDL对内皮依赖性血管舒张和早期内皮祖细胞介导的内皮修复的影响。糖尿病患者被随机分配到3个月的治疗与ER烟酸（1500毫克/天）或安慰剂，HDL的内皮效应的特点。来自健康受试者的HDL刺激内皮一氧化氮产生，降低内皮氧化应激，改善内皮依赖性血管舒张和早期内皮祖细胞介导的内皮修复。与此相反，这些有益的内皮细胞的HDL的影响，没有观察到在HDL糖尿病患者，这表明显着受损的内皮细胞保护特性的HDL。ER烟酸治疗提高了HDL刺激内皮一氧化氮的能力，减少超氧化物的产生，并促进内皮祖细胞介导的内皮修复。进一步的测量表明，增加的HDL在糖尿病患者的脂质氧化，并减少ER烟酸therapy. Conclusions-HDL从2型糖尿病和代谢综合征患者的血管内皮保护作用与HDL从健康受试者相比，大大受损。ER烟酸治疗不仅增加HDL血浆水平，但显着改善这些患者的HDL的内皮保护功能，这可能是更重要的。
Background-High-density lipoprotein (HDL)-raising therapies are currently under intense evaluation, but the effects of HDL may be highly heterogeneous. We therefore compared the endothelial effects of HDL from healthy subjects and from patients with type 2 diabetes mellitus and low HDL (meeting the criteria for metabolic syndrome), who are frequently considered for HDL-raising therapies. Moreover, in diabetic patients, we examined the impact of extended-release (ER) niacin therapy on the endothelial effects of HDL.Methods and Results-HDL was isolated from healthy subjects (n = 10) and patients with type 2 diabetes (n = 33) by sequential ultracentrifugation. Effects of HDL on endothelial nitric oxide and superoxide production were characterized by electron spin resonance spectroscopy analysis. Effects of HDL on endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair were examined. Patients with diabetes were randomized to a 3-month therapy with ER niacin (1500 mg/d) or placebo, and endothelial effects of HDL were characterized. HDL from healthy subjects stimulated endothelial nitric oxide production, reduced endothelial oxidant stress, and improved endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair. In contrast, these beneficial endothelial effects of HDL were not observed in HDL from diabetic patients, which suggests markedly impaired endothelial-protective properties of HDL. ER niacin therapy improved the capacity of HDL to stimulate endothelial nitric oxide, to reduce superoxide production, and to promote endothelial progenitor cell-mediated endothelial repair. Further measurements suggested increased lipid oxidation of HDL in diabetic patients, and a reduction after ER niacin therapy.Conclusions-HDL from patients with type 2 diabetes mellitus and metabolic syndrome has substantially impaired endothelial-protective effects compared with HDL from healthy subjects. ER niacin therapy not only increases HDL plasma levels but markedly improves endothelial-protective functions of HDL in these patients, which is potentially more important.