在血浆低密度脂蛋白胆固醇水平正常的高甘油三酯血症患者中，乙酰胆碱介导的内皮依赖性舒张功能受损。

Endothelium-dependent relaxation by acetylcholine is impaired in hypertriglyceridemic humans with normal levels of plasma LDL cholesterol.

作者信息

Lewis T V, Dart A M, Chin-Dusting J P

机构信息

Alfred and Baker Medical Unit, Baker Medical Research Institute and The Alfred Hospital, Prahran, Victoria, Australia.

出版信息

J Am Coll Cardiol. 1999 Mar;33(3):805-12. doi: 10.1016/s0735-1097(98)00667-6.

DOI:10.1016/s0735-1097(98)00667-6

PMID:10080485

Abstract

OBJECTIVES

Patients with high triglyceride (of which very low density lipoproteins [VLDL] are the main carriers), but with normal low density lipoprotein (LDL) cholesterol levels, were examined for in vivo endothelium function status.

BACKGROUND

Very low density lipoproteins inhibit endothelium-dependent, but not -independent, vasorelaxation in vitro.

METHODS

Three groups were studied: 1) healthy volunteers (n = 10; triglyceride 1.24+/-0.14 mmol/liter, LDL cholesterol 2.99+/-0.24 mmol/liter); 2) hypertriglyceridemic (n = 11; triglyceride 6.97+/-1.19 mmol/liter, LDL cholesterol 2.17+/-0.2 mmol/liter, p < 0.05); and 3) hypercholesterolemic (n = 10; triglyceride 2.25+/-0.29 mmol/liter, LDL cholesterol 5.61+/-0.54 mmol/liter; p < 0.05) patients. Vasoactive responses to acetylcholine, sodium nitroprusside, noradrenaline, N(G)-monomethyl-L-arginine and postischemic hyperemia were determined using forearm venous occlusion plethysmography.

RESULTS

Responses to acetylcholine (37 microg/min) were significantly dampened both in hypercholesterolemic (% increase in forearm blood flow: 268.2+/-62) and hypertriglyceridemic patients (232.6+/-45.2) when compared with controls (547.8+/-108.9; ANOVA p < 0.05). Responses to sodium nitroprusside (at 1.6 microg/min: controls vs. hypercholesterolemics vs. hypertriglyceridemic: 168.7+/- 25.1 vs. 140.6+/-38.9 vs. 178.5+/-54.5% increase), noradrenaline, N(G)-monomethyl-L-arginine and postischemic hyperemic responses were not different among the groups examined.

CONCLUSIONS

Acetylcholine responses are impaired in patients with pathophysiologic levels of plasma triglycerides but normal plasma levels of LDL cholesterol. The impairment observed was comparable to that obtained in hypercholesterolemic patients. We conclude that impaired responses to acetylcholine normally associated with hypercholesterolemia also occur in hypertriglyceridemia. These findings identify a potential mechanism by which high plasma triglyceride levels may be atherogenic independent of LDL cholesterol levels.

摘要

目的

对甘油三酯水平高（其中极低密度脂蛋白[VLDL]是主要载体）但低密度脂蛋白（LDL）胆固醇水平正常的患者进行体内内皮功能状态检查。

背景

极低密度脂蛋白在体外可抑制内皮依赖性而非非依赖性血管舒张。

方法

研究了三组：1）健康志愿者（n = 10；甘油三酯1.24±0.14 mmol/升，LDL胆固醇2.99±0.24 mmol/升）；2）高甘油三酯血症患者（n = 11；甘油三酯6.97±1.19 mmol/升，LDL胆固醇2.17±0.2 mmol/升，p < 0.05）；3）高胆固醇血症患者（n = 10；甘油三酯2.25±0.29 mmol/升，LDL胆固醇5.61±0.54 mmol/升；p < 0.05）。使用前臂静脉闭塞体积描记法测定对乙酰胆碱、硝普钠、去甲肾上腺素、N(G)-单甲基-L-精氨酸和缺血后充血的血管活性反应。

结果

与对照组（547.8±108.9；方差分析p < 0.05）相比，高胆固醇血症患者（前臂血流量增加百分比：268.2±62）和高甘油三酯血症患者（232.6±45.2）对乙酰胆碱（37微克/分钟）的反应均明显减弱。对硝普钠（1.6微克/分钟时：对照组与高胆固醇血症组与高甘油三酯血症组：增加百分比分别为168.7±25.1、140.6±38.9、178.5±54.5）、去甲肾上腺素、N(G)-单甲基-L-精氨酸和缺血后充血反应在各研究组之间无差异。

结论

血浆甘油三酯处于病理生理水平但血浆LDL胆固醇水平正常的患者对乙酰胆碱的反应受损。观察到的损伤与高胆固醇血症患者的损伤相当。我们得出结论，高甘油三酯血症也会出现通常与高胆固醇血症相关的对乙酰胆碱反应受损的情况。这些发现确定了一种潜在机制，通过该机制高血浆甘油三酯水平可能独立于LDL胆固醇水平而具有致动脉粥样硬化作用。