Serotonin receptors and ischemic heart disease

我们研究了5-羟色胺（5-HT）及其受体在动脉粥样硬化和缺血性心脏病发病中的作用。研究结果如下：5- ht引起的动脉粥样硬化血管收缩异常我们同时测量了Watanabe遗传性高脂血症（WHHL）兔主动脉的等长张力和细胞内Ca^<2+>。虽然5-HT诱导的正常主动脉收缩被酮色胺完全阻断，但WHHL兔的动脉粥样硬化性动脉对5-HT表现出酮色胺抵抗性的过度收缩，提示5- ht1样受体的参与。Ca^<2+>的动员增强，而Ca^<2+>对收缩成分的敏感性没有改变，这伴随着对5-HT.2的收缩反应增强。采用从人死后冠状动脉中提取的总RNA进行RNase保护实验，对人冠状动脉（HCA）中5-HT受体进行分子分析，以明确HCA中5-HT受体亚型。5-HT1Dbeta和5-HT2A受体mRNA在HCA中主要表达，5-HT1Dbeta受体mRNA在HCA合并动脉粥样硬化中表达上调。这些发现表明，通过5- ht1dβ受体介导的收缩可能在动脉粥样硬化hca对5-HT的增强收缩反应中起重要作用。急性心肌梗死（AMI）与5-HT2A受体基因多态性研究了AMI与5-HT2A受体T^<102> C多态性的关系。AMI患者TT和TC基因型频率显著增高。提示5-HT2A受体基因多态性可能是AMI的独立危险因素。

We have studied the involvement of serotonim (5-HT) and its receptor in the pathogenesis of atherosclerosis and ischemic heart disease. The relults are as follow ;1.Abnormality in 5-HT-evoked contraction in atherosclerotic vesslsWe measured simultaneously isometric tension and intracellular Ca^<2+> in aortae from Watanabe Hereditary Hyperlipidemic (WHHL) rabbits. Although 5-HT-induced contraction in normal aorta was completely blocked by ketanserin, atherosclerotic arora from WHHL rabbits exhibited ketanserin-resistant hypercontraction to 5-HT,suggesting the involvement of 5-HT1-like receprors. The augmented Ca^<2+> mobilization but no the altered Ca^<2+> sensitivity of contractile component was accompanied by this augmented contratile response to 5-HT.2.Molecular analysis of 5-HT receptors in human coronary artery (HCA)RNase protection assay was performed using total RNA extracted from post-mortem human coronary arteries to clarify 5-HT receptor subtypes in HCA.It revealed the predominant expression of 5-HT1Dbeta and 5-HT2A receptors mRNA in HCA.5-HT1Dbeta receptor mRNA was upregulated in HCA with atherosclerosis. These findings suggest that contraction mediated through 5-HT1Dbeta receptor might play an important role in the augmented contractile respomse to 5-HT in atherosclerotic HCA.3.Acute myocardial infarction (AMI) and polymorphism of 5-HT2A receptor geneWe examined the association between AMI and 5-HT2A receptor T^<102> C polymorphism. Frequency of TT and TC genotype was significantly increased in patients with AMI.Our findings indicate that polymorphism of 5-HT2A receptor gene may be an independent risk factor of AMI.