Serotonin receptors and ischemic heart disease

血清素受体与缺血性心脏病

• 批准号: 07557345
• 负责人: YOKOYAMA Mitsuhiro
• 金额: $ 2.3万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557345/
• 关键词: serotonin; coronary spasm; atherosclerosis; vascular smooth muscle; molecular biology; intracellular calcium; acute myocardial infarction; polymorphism; 遺伝子多型性

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.

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。结果如下：1.动脉粥样硬化血管5-HT诱发收缩的异常我们同时测定了Watanabe遗传性高脂血症（WHHL）家兔动脉的等长收缩张力和细胞内Ca ~（2+）。酮色林能完全阻断5-HT对正常主动脉的收缩作用，但WHHL兔动脉粥样硬化动脉对5-HT的收缩反应不受酮色林的影响，提示有5-HT 1样受体参与。2.人冠状动脉（HCA）中5-HT受体的分子生物学分析采用从人死后冠状动脉中提取的总RNA进行RNA酶保护试验，以阐明HCA中5-HT受体的亚型，结果显示HCA中5-HT受体的主要表达是5-HT受体亚型。HCA中5-HT 1D β和5-HT 2A受体mRNA的表达，HCA伴动脉粥样硬化时5-HT 1D β受体mRNA表达上调。提示5-HT_（1D）β受体介导的心肌收缩可能在动脉粥样硬化性HCA对5-HT的收缩反应增强中起重要作用。3.急性心肌梗死（AMI）与5-HT_（2A）受体基因多态<102>性AMI患者TT和TC基因型频率明显增高，提示5-HT_2A受体基因多态性可能是AMI的独立危险因素。

项目成果

Ken-ichi Hirata: "Low concentration of oxidized low density lipoprotein and lysophospatidylcholine upergulate constitutive nitric oxdie synthase mRNA expression in bovine aortic endothelial cells." Circulation Research. 76. 958-962 (1995)

Ken-ichi Hirata：“低浓度的氧化低密度脂蛋白和溶血磷脂酰胆碱上调牛主动脉内皮细胞中组成型一氧化氮合酶 mRNA 表达。”

Kenji Kanazawa: "Endothelial constitutive nitric oxide synthase protein and mRNA were increased in atheosclerotic aorta despite of impaired endothelium-dependent vasular relaxation." American Joural of Pathology. 148. 1949-1956 (1995)

Kenji Kanazawa：“尽管内皮依赖性血管舒张受损，但动脉粥样硬化主动脉中的内皮组成型一氧化氮合酶蛋白和 mRNA 仍增加。”

Seinsuke Kawashima: "Cardiac-Vascular Remodeling and Functional Interaction" Nitric oxide and the heart : Implication in physiological and pathological conditions in Cardiac-vascular remodeling and functional interaction., 402 (1995)

Seinsuke Kawashima：“心脏血管重塑和功能相互作用”一氧化氮和心脏：对心血管重塑和功能相互作用的生理和病理条件的影响。，402（1995）

Mitsuhiro Yokoyama: "Serotonin in the Central Nervous System and Periphery" Role of serotonin in the pathophysiology of coronary artery disease, 260 (1995)

Mitsuhiro Yokoyama：“血清素在中枢神经系统和外周中的作用”血清素在冠状动脉疾病的病理生理学中的作用，260（1995）

Yoshihiro Ikeda: "Nitric ixde synthase isoform activies in kidey of Dahl saly-senditive rats." Hypertension. 26. 1030-1034 (1995)

Yoshihiro Ikeda：“Dahl saly 敏感大鼠肾脏中的一氧化氮合酶异构体活性。”