Department of Cardiovascular Physiology and Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Am J Physiol Endocrinol Metab. 2010 Feb;298(2):E202-9. doi: 10.1152/ajpendo.00394.2009. Epub 2009 Nov 10.
Epidemiologic studies have shown that a low level of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular diseases. The purpose of this study was to determine the contribution of isolated low HDL cholesterol to endothelial function. Thirty-nine subjects with low HDL cholesterol who had no other cardiovascular risk factors were selected from the 5,417 participants from our population. We evaluated flow-mediated vasodilation (FMD) before and after 4 wk of treatment with the HMG-CoA reductase inhibitor pravastatin in 29 of the 39 subjects with isolated low HDL cholesterol. FMD was lower in the low-HDL-cholesterol group (n = 29) than in the control group (n = 29), whereas NTG-induced vasodilation was similar in the two groups. Pravastatin increased HDL cholesterol, urinary excretion of nitrite/nitrate, circulating levels of progenitor cells, and cell migration response to vascular endothelial growth factor in 15 subjects with low HDL cholesterol but not in 14 placebo control subjects. FMD increased in the pravastatin treatment group but not in the control group. NTG-induced vasodilation was similar before and after 4 wk of treatment in the two groups. Multiple regression analysis revealed that changes in HDL cholesterol, the number of progenitor cells, and migration of progenitor cells were independent predictors of augmentation of FMD with pravastatin. These findings suggest that low HDL cholesterol is an independent risk factor for endothelial dysfunction and that pravastatin improves endothelial function in individuals with isolated low HDL cholesterol through, at least in part, an increase in circulating progenitor cells.
流行病学研究表明，低水平的高密度脂蛋白（HDL）胆固醇是心血管疾病的一个危险因素。本研究的目的是确定孤立性低 HDL 胆固醇对血管内皮功能的影响。从我们的人群中 5417 名参与者中，选择了 39 名无其他心血管危险因素的低 HDL 胆固醇患者，评估他们在接受 HMG-CoA 还原酶抑制剂普伐他汀治疗 4 周前后的血流介导的血管扩张（FMD）。在 29 名孤立性低 HDL 胆固醇患者中，低 HDL 胆固醇组（n = 29）的 FMD 低于对照组（n = 29），而两组的 NTG 诱导的血管扩张相似。普伐他汀增加了 15 名低 HDL 胆固醇患者的 HDL 胆固醇、亚硝酸盐/硝酸盐尿排泄、循环祖细胞水平和对血管内皮生长因子的细胞迁移反应，但对 14 名安慰剂对照患者没有影响。FMD 在普伐他汀治疗组增加，但在对照组没有增加。两组在治疗 4 周前后的 NTG 诱导的血管扩张相似。多元回归分析显示，HDL 胆固醇、祖细胞数量和祖细胞迁移的变化是 FMD 随普伐他汀治疗增加的独立预测因子。这些发现表明，低 HDL 胆固醇是血管内皮功能障碍的独立危险因素，普伐他汀通过至少部分增加循环祖细胞，改善了孤立性低 HDL 胆固醇个体的内皮功能。
