Capell Warren H, DeSouza Christopher A, Poirier Paul, Bell Melanie L, Stauffer Brian L, Weil Kathleen M, Hernandez Teri L, Eckel Robert H
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):307-13. doi: 10.1161/01.atv.0000046230.02211.b4.
The objective of this study was to investigate the effects of lowering plasma triglycerides (TGs) on endothelial function and gain insight into the role played by free fatty acids (FFAs) in hypertriglyceridemia-associated vascular dysfunction.
Eleven hypertriglyceridemic subjects without coronary artery disease, diabetes, elevated low-density lipoprotein cholesterol, tobacco use, or hypertension were studied using a randomized, double-blinded, crossover design (fenofibrate and placebo, 14 days). After each regimen, forearm blood flow was assessed by plethysmography in response to arterial acetylcholine, nitroprusside, and verapamil infusion. Hourly plasma TGs, FFA, glucose, and insulin were measured during a 24-hour feeding cycle to characterize the metabolic environment. Changes in plasma FFA after intravenous heparin were used to estimate typical FFA accumulation in the luminal endothelial microenvironment. Fenofibrate lowered plasma TG (P<0.001), total cholesterol (P<0.01), and apolipoprotein B (P<0.01) without altering high-density lipoprotein or low-density lipoprotein cholesterol concentrations. Forearm blood flow in response to acetylcholine (P<0.0001), nitroprusside (P<0.001), and verapamil (P<0.0001) improved after fenofibrate. Fenofibrate lowered 24-hour (P<0.0001) and post-heparin (P<0.001) TG and tended to lower 24-hour (P=0.054) and post-heparin (P=0.028) FFA.
Vascular smooth muscle function significantly improves after lowering plasma TG without changes in confounding lipoproteins or insulin resistance. The data raise additional questions regarding the role of FFA in hypertriglyceridemia-associated vascular dysfunction.
本研究旨在探讨降低血浆甘油三酯（TGs）对内皮功能的影响，并深入了解游离脂肪酸（FFAs）在高甘油三酯血症相关血管功能障碍中所起的作用。
采用随机、双盲、交叉设计（非诺贝特和安慰剂，14天），对11名无冠状动脉疾病、糖尿病、低密度脂蛋白胆固醇升高、吸烟或高血压的高甘油三酯血症患者进行研究。每种治疗方案后，通过体积描记法评估前臂血流，以响应动脉注射乙酰胆碱、硝普钠和维拉帕米。在24小时进食周期内每小时测量血浆TG、FFA、葡萄糖和胰岛素，以表征代谢环境。静脉注射肝素后血浆FFA的变化用于估计管腔内内皮微环境中典型的FFA积累。非诺贝特降低了血浆TG（P<0.001）、总胆固醇（P<0.01）和载脂蛋白B（P<0.01），而未改变高密度脂蛋白或低密度脂蛋白胆固醇浓度。非诺贝特治疗后，对乙酰胆碱（P<0.0001）、硝普钠（P<0.001）和维拉帕米（P<0.0001）的前臂血流得到改善。非诺贝特降低了24小时（P<0.0001）和肝素后（P<0.001）的TG，并倾向于降低24小时（P=0.054）和肝素后（P=0.028）的FFA。
降低血浆TG后，血管平滑肌功能显著改善，而混杂脂蛋白或胰岛素抵抗无变化。这些数据引发了关于FFA在高甘油三酯血症相关血管功能障碍中作用的更多问题。
