The role of inflammatory mechanisms in the pathogenesis of ischemic heart disease. Basic and clinical studies.

炎症机制在缺血性心脏病发病机制中的作用。

• 批准号: 07457173
• 负责人: SHIMOKAWA Hiroaki
• 金额: $ 4.42万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-07457173/
• 关键词: inflammatory cytokine; ischemic heart disease; arteriosclerosis; coronary spasm; coronary thrombosis; myocardial infarction; サイトカイン; 細胞増殖因子; 冠動脈硬化; 冠動撃縮

We have obtained many important findings regarding the role of inflammatory mechanisms in the pathogenesis of coronary arteriosclerosis and ischemic heart disease.(1) Chronic treatment with interleukin-1beta (IL-1beta) causes remodeling, neointimal formation, and vasospastic responses of the coronary artery in pigs in vivo.(2) The same changes of the coronary artery were also noted by the chronic treatment with other major inflammatory cytokines, such as IL-1alpha and tumor necrosis factor-alpha, with the alterations in myosin heavy chain isoforms toward de-differentiation.(3) The IL-1beta-induced changes of the coronary artery were mediated by platelet-derived growth factor and fibroblast growth factor-2 in vivo.(4) The IL-1beta-induced changes of the coronary artery were markedly inhibited by cotreatment with ST 638, a specific inhibitor of tyrosine kinases, indicating the important role of tyrosine kinase activation in the pathogenesis of coronary arteriosclerosis in vivo.(5) The intracellular pathway mediated by protein kinase C (PKC) was substantially involved in the pathogenesis of coronary spasm at the arteriosclerotic lesions in vivo.(6) During the course of acute myocardial infaction, the plasma levels of some cytokines temporarily increased, while those of other cytokines were increased for a longer period.

关于炎症机制在冠状动脉硬化和缺血性心脏病发病机制中的作用，我们已经获得了许多重要的发现。（1）白细胞介素-1β（IL-1β）的长期治疗会导致冠状动脉的重塑、新生内膜形成和血管痉挛反应(2)其他主要炎症细胞因子如IL-1α和肿瘤坏死的长期治疗也观察到了冠状动脉的相同变化。 (3) IL-1β 诱导的冠状动脉变化是由体内血小板衍生生长因子和成纤维细胞生长因子 2 介导的。(4 ) 与酪氨酸激酶特异性抑制剂 ST 638 联合治疗可显着抑制 IL-1β 诱导的冠状动脉变化，表明酪氨酸激酶激活在冠状动脉发病机制中的重要作用(5)蛋白激酶C(PKC)介导的细胞内通路实质上参与了体内动脉硬化病变处冠状动脉痉挛的发病机制。(6)急性心肌梗死病程中血浆中一些细胞因子暂时升高，而另一些细胞因子则长期升高。

项目成果

Kadokami T,Shimokawa H,Fukumoto Y,et al.: "Coronary artery spasm does not depend on the intracellular calcimum store but is substantially mediated by the protein kinase C-mediated pathway in a swine model with interleukin-1beta in vivo." Circulation. 94.

Kadokami T、Shimokawa H、Fukumoto Y 等人：“在体内白细胞介素 1β 的猪模型中，冠状动脉痉挛并不依赖于细胞内钙储存，而是基本上由蛋白激酶 C 介导的途径介导。”

Fukumoto Y et al.: "Tyrosine kinase inhibitor suppresses the(re)stenotic changes of the coronary artery……" Cardiovascular Research. 32. 1131-1140 (1996)

Fukumoto Y 等人：“酪氨酸激酶抑制剂抑制冠状动脉的（再）狭窄变化……”心血管研究。32. 1131-1140 (1996)

Fukumoto Y,Shimokawa H,Kozai T,et al.: "Tyrosine kinase inhibitor suppresses the (re) stenotic changes of the coronary artery after balloon injury in pigs." Cardiovascular Research. 32. 1131-1140 (1996)

Fukumoto Y、Shimokawa H、Kozai T 等人：“酪氨酸激酶抑制剂可抑制猪球囊损伤后冠状动脉的（再）狭窄变化。”

Kadokami T et al.: "Coronary artery sposm does not depend on the intracellular cacium store but is substantially mediated by the protein kinase-C modiated pathway-" Circulation. (in press).

Kadokami T 等人：“冠状动脉精子不依赖于细胞内钙的储存，而是基本上由蛋白激酶 C 调节的途径介导”循环。

Shimokawa H et al.: "Chronic treatment with interleukin-1β induces coronary intimal tesions and vasospostic responses in pigs in vivo." J Clin Invest. (in press).

Shimokawa H 等人：“白细胞介素 1β 的长期治疗可诱导猪体内冠状动脉内膜张力和血管后缩反应。”（J Clin Invest）。