Spieker Lukas E, Sudano Isabella, Hürlimann David, Lerch Peter G, Lang Markus G, Binggeli Christian, Corti Roberto, Ruschitzka Frank, Lüscher Thomas F, Noll Georg
Cardiology, University Hospital, Zürich, Switzerland.
Circulation. 2002 Mar 26;105(12):1399-402. doi: 10.1161/01.cir.0000013424.28206.8f.
Hypercholesterolemia is a risk factor for atherosclerosis-causing endothelial dysfunction, an early event in the disease process. In contrast, high-density lipoprotein (HDL) cholesterol inversely correlates with morbidity and mortality representing a protective effect. Therefore, we investigated the effects of reconstituted HDL on endothelial function in hypercholesterolemic men.
Endothelium-dependent and -independent vasodilation to intraarterial acetylcholine and sodium nitroprusside (SNP), respectively, was measured by forearm venous occlusion plethysmography in healthy normo- and hypercholesterolemic men. In hypercholesterolemics, the effects of reconstituted HDL (rHDL; 80 mg/kg IV over 4 hours) on acetylcholine- and SNP-induced changes in forearm blood flow were assessed in the presence or absence of the nitric oxide (NO) synthase inhibitor L-NMMA. Hypercholesterolemics showed reduced vasodilation to acetylcholine but not to SNP compared with normocholesterolemics (P<0.0001). rHDL infusion increased plasma HDL cholesterol from 1.3+/-0.1 to 2.2+/-0.1 mmol/L (P<0.0001, n=18) and significantly enhanced the acetylcholine-induced increase in forearm blood flow without affecting that induced by SNP. rHDL infusion also improved flow-mediated dilation of the brachial artery (to 4.5+/-0.9% from 2.7+/-0.6%, P=0.02). NO synthase inhibition prevented the improvement in acetylcholine-induced vasodilation while leaving the response to SNP unchanged. Albumin infusion in an equivalent protein dose had no effect on vasomotion or lipid levels.
In hypercholesterolemic patients, intravenous rHDL infusion rapidly normalizes endothelium-dependent vasodilation by increasing NO bioavailability. This may in part explain the protective effect of HDL from coronary heart disease and illustrates the potential therapeutic benefit of increasing HDL in patients at risk from atherosclerosis.
高胆固醇血症是导致动脉粥样硬化引起内皮功能障碍的危险因素，内皮功能障碍是疾病进程中的早期事件。相比之下，高密度脂蛋白（HDL）胆固醇与发病率和死亡率呈负相关，具有保护作用。因此，我们研究了重组HDL对高胆固醇血症男性内皮功能的影响。
通过前臂静脉阻塞体积描记法分别测量健康正常和高胆固醇血症男性对动脉内乙酰胆碱和硝普钠（SNP）的内皮依赖性和非内皮依赖性血管舒张。在高胆固醇血症患者中，在存在或不存在一氧化氮（NO）合酶抑制剂L-NMMA的情况下，评估重组HDL（rHDL；4小时内静脉注射80mg/kg）对乙酰胆碱和SNP诱导的前臂血流变化的影响。与正常胆固醇血症患者相比，高胆固醇血症患者对乙酰胆碱的血管舒张作用降低，但对SNP的血管舒张作用未降低（P<0.0001）。rHDL输注使血浆HDL胆固醇从1.3±0.1mmol/L增加到2.2±0.1mmol/L（P<0.0001，n=18），并显著增强了乙酰胆碱诱导的前臂血流增加，而不影响SNP诱导的血流增加。rHDL输注还改善了肱动脉的血流介导的舒张（从2.7±0.6%改善到4.5±0.9%，P=0.02）。NO合酶抑制可防止乙酰胆碱诱导的血管舒张改善，而对SNP的反应保持不变。等量蛋白质剂量的白蛋白输注对血管运动或血脂水平无影响。
在高胆固醇血症患者中，静脉输注rHDL通过增加NO生物利用度迅速使内皮依赖性血管舒张恢复正常。这可能部分解释了HDL对冠心病的保护作用，并说明了在有动脉粥样硬化风险的患者中增加HDL的潜在治疗益处。
