高密度脂蛋白的血管内皮保护作用在 2 型糖尿病患者中受损，但经烟酸缓释治疗后可得到改善。

Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy.

机构信息

Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.

出版信息

Circulation. 2010 Jan 5;121(1):110-22. doi: 10.1161/CIRCULATIONAHA.108.836346. Epub 2009 Dec 21.

DOI:10.1161/CIRCULATIONAHA.108.836346

PMID:20026785

Abstract

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.

CLINICAL TRIAL REGISTRATION

clinicaltrials.gov. Identifier: NCT00346970.

摘要

背景

目前，人们正在深入评估能升高高密度脂蛋白（HDL）的疗法，但 HDL 的作用可能存在很大差异。因此，我们比较了健康受试者和 2 型糖尿病伴低 HDL（符合代谢综合征标准）患者的 HDL 的内皮细胞效应，这些患者通常需要进行 HDL 升高治疗。此外，在糖尿病患者中，我们还研究了延长释放（ER）烟酸治疗对 HDL 内皮细胞效应的影响。

方法和结果

通过连续超速离心从健康受试者（n=10）和 2 型糖尿病患者（n=33）中分离 HDL。通过电子自旋共振光谱分析来描述 HDL 对内皮一氧化氮和超氧化物产生的影响。检测了 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作用。将糖尿病患者随机分为 ER 烟酸（1500 mg/d）或安慰剂治疗 3 个月，并对 HDL 的内皮细胞效应进行了特征描述。健康受试者的 HDL 刺激内皮一氧化氮产生，减少内皮氧化应激，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。相比之下，在糖尿病患者的 HDL 中，这些有益的 HDL 内皮细胞效应并未观察到，这表明 HDL 的内皮保护特性明显受损。ER 烟酸治疗改善了 HDL 刺激内皮一氧化氮产生、减少超氧化物产生和促进内皮祖细胞介导的内皮修复的能力。进一步的测量表明，糖尿病患者的 HDL 脂质氧化增加，而 ER 烟酸治疗后则减少。