Role of Inflammatory Cytokines in the Development and Progression of Ischemic Heart Diseases-Experimental and Clinical Studies-

炎症细胞因子在缺血性心脏病发生和进展中的作用-实验和临床研究-

• 批准号: 05454274
• 负责人: SHIMOKAWA Hiroaki
• 金额: $ 4.22万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454274/
• 关键词: inflammatory cytokines; ischemic heart disease; arteriosclerosis; coronary artery spasm; coronary thrombosis; myocardial infarction; サイトカイン; 細胞増殖因子; 冠動脈硬化; 冠等縮; 冠□縮

(A)Basic Research(1) Chrocic Treatment with interleukin (IL) -1beta causes arteriosclerotic changes and vasospastic responses to autacoids in porcine coronary arteries in vivo.(2) Chronic treatment with IL-1alpha or tumor necrosis factor-alpha (TNF-alpha) also caused similar changes of the coronary artery, showing the redundant effects of inflammatory cytokines.(3) The histological and functiona changes of the coronary artery induced by IL-1beta were mediated by both platelet-derived growth factor and fibroblast growth factor-2.(4) A selective tyrosine kinase inhibitor, ST638, markedly suppressed the histological and functional changes of the coronary artery induced by IL-1beta.(5) In the pathogenesis of coronary artery spasm at the inflammatory coronary lesions, a PKC-mediated pathway plays an important role, while the contribution of Ca^<2+>release from the intracellular store site may be minimal.(B)Clinical Research(6) Three types of changes in the plasma levels of cytokines were noted in patients with acute myocardial infarction ; transient increase (plasma levels of IL-6, generation capacity for IL-1alpha), sustained increase (plasma levels of macrophagecolony stimulating factor and generation capacity for IL-1beta), and late increase (plasma levels of interferon-gamma).(7) In patients with ischemic heart disease, plasma levels of macrophage colony stimulating factor were increased, while those of transforming growth factor-beta were decreased.

（A）基础研究（1）在活体猪的冠状动脉中，用白细胞介素（IL）-1 β进行Chrocic处理，引起动脉炎性改变和对自体激素的血管痉挛反应。(2)IL-1 α或肿瘤坏死因子-α（TNF-alpha）的长期治疗也会引起冠状动脉的类似变化，表明炎症细胞因子的多余作用。(3)IL-1 β诱导的冠状动脉组织学和功能改变是由血小板源性生长因子和成纤维细胞生长因子2共同介导的。(4)选择性酪氨酸激酶抑制剂ST 638可明显抑制IL-1 β诱导的冠状动脉组织学和功能变化。(5)在炎症性冠状动脉病变处冠状动脉痉挛的发病机制中，PKC介导的通路起着重要作用，而细胞内储存位点的Ca^2+释放的贡献可能很小。（B）临床研究（6）在急性心肌梗死患者中观察到三种类型的细胞因子血浆水平的变化：瞬时增加（IL-6的血浆水平、IL-1 α的产生能力）、持续增加（巨噬细胞集落刺激因子的血浆水平和IL-1 β的产生能力）和晚期增加（干扰素-γ的血浆水平）。(7)在缺血性心脏病患者中，巨噬细胞集落刺激因子的血浆水平升高，而转化生长因子-β的血浆水平降低。

项目成果

Shimokawa H,Takeshita A.: "Endothelium dependent regulation of the cardiovascular system." Intern Med. 34. 939-946 (1995)

Shimokawa H，Takeshita A.：“心血管系统的内皮依赖性调节。”

Ito A.,et al.: "Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm" Circulation. 90. 2425-2431 (1994)

Ito A.,et al.：“蛋白激酶 C 介导的途径在冠状动脉痉挛发病机制中的作用”循环。

Tashiro H.: "clinical characteristics of patients with spontaneous remission of variant angina." Japanese Circulation Jouinal. 57. 117-122 (1993)

Tashiro H.：“变异型心绞痛自发缓解患者的临床特征。”

Shimokawa H.et al.: "Significance of defective endothelial signal transduction in impaired endothelium-dependent relaxation in atherosclerosis." Gerontology.41. 28-33 (1995)

Shimokawa H.等人：“内皮信号转导缺陷在动脉粥样硬化中内皮依赖性舒张受损中的意义。”

Shimokawa H,Ito A,Fukumoto Y.et al.: "Chronic treatment with Interleukin-1beta induces coronary intimal lesions and vasospastic responses in pigs in vivo." J Clin Invest.97. 769-776 (1996)

Shimokawa H、Ito A、Fukumoto Y.等人：“白细胞介素-1β 的长期治疗会在猪体内诱导冠状动脉内膜损伤和血管痉挛反应。”