Lentz S R, Sobey C G, Piegors D J, Bhopatkar M Y, Faraci F M, Malinow M R, Heistad D D
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
J Clin Invest. 1996 Jul 1;98(1):24-9. doi: 10.1172/JCI118771.
Elevated plasma homocyst(e)ine may predispose to complications of vascular disease. Homocysteine alters vasomotor regulatory and anticoagulant properties of cultured vascular endothelial cells, but little is known about effects of hyperhomocyst(e)inemia on vascular function in vivo. We tested the hypothesis that diet-induced moderate hyperhomocyst(e)inemia is associated with vascular dysfunction in cynomolgus monkeys. Plasma homocyst(e)ine increased from 4.O +/- O.2 microM when monkeys were fed normal diet to 10.6 +/- 2.6 microM when they were fed modified diet (mean +/- SE; P = 0.02). Vasomotor responses were assessed in vivo by quantitative angiography and Doppler measurement of blood flow velocity. In response to activation of platelets by intraarterial infusion of collagen, blood flow to the leg decreased by 42 +/- 9% in monkeys fed modified diet, compared with 14 +/- 11% in monkeys fed normal diet (P = 0.008), Responses of resistance vessels to the endothelium-dependent vasodilators acetylcholine and ADP were markedly impaired in hyperhomocyst(e)inemic monkeys, which suggests that increased vasoconstriction in response to collagen may be caused by decreased vasodilator responsiveness to platelet-generated ADP. Relaxation to acetylcholine and, to a lesser extent, nitroprusside, was impaired ex vivo in carotid arteries from monkeys fed modified diet. Thrombomodulin anticoagulant activity in aorta decreased by 34 +/- 15% in hyperhomocyst(e)inemic monkeys (P = 0.03). We conclude that diet-induced moderate hyperhomocyst(e)inemia is associated with altered vascular function.
血浆同型半胱氨酸水平升高可能易引发血管疾病并发症。同型半胱氨酸会改变培养的血管内皮细胞的血管舒缩调节和抗凝特性，但关于高同型半胱氨酸血症对体内血管功能的影响却知之甚少。我们检验了这样一个假设，即饮食诱导的中度高同型半胱氨酸血症与食蟹猴的血管功能障碍有关。当猴子喂食正常饮食时，血浆同型半胱氨酸水平从4.0±0.2微摩尔/升增加到喂食改良饮食时的10.6±2.6微摩尔/升（平均值±标准误；P = 0.02）。通过定量血管造影和多普勒测量血流速度在体内评估血管舒缩反应。经动脉内注入胶原蛋白激活血小板后，喂食改良饮食的猴子腿部血流量减少了42±9%，而喂食正常饮食的猴子减少了14±11%（P = 0.008）。高同型半胱氨酸血症的猴子中，阻力血管对内皮依赖性血管舒张剂乙酰胆碱和ADP的反应明显受损，这表明对胶原蛋白反应时血管收缩增加可能是由于对血小板生成的ADP的血管舒张反应性降低所致。喂食改良饮食的猴子离体颈动脉对乙酰胆碱以及在较小程度上对硝普钠的舒张反应受损。高同型半胱氨酸血症的猴子主动脉中血栓调节蛋白的抗凝活性降低了34±15%（P = 0.03）。我们得出结论，饮食诱导的中度高同型半胱氨酸血症与血管功能改变有关。
