Role of Rho/Rho-kinase-mediated pathway in the pathogenesls of atherosclerosis

Rho/Rho激酶介导的通路在动脉粥样硬化发病机制中的作用

• 批准号: 13307024
• 负责人: SHIMOKAWA Hiroaki
• 金额: $ 35.19万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13307024/
• 关键词: Rho-kinase; Vasospastic angina; Atherosclerosis; Cardiac hypertrophy; Restenosis; Myocardial infarction; Heart failure; Pulmonary hypertension; Rho-kinase; Rho; 炎症; 狭心症; シグナル伝達; 冠動脈攣縮; 高血圧

(1)We have demonstrated that Rho/Rho-kinase-mediated pathway plays an important role in the pathogenesis of hypertension.(2)We have demonstrated that Rho-kinase-mediated pathway is substantially involved in the pathogenesis of angiotensin II-induced cardiovascular hypertrophy in rats.(3)We have demonstrated that Rho-kinase is located downstream of PKC in the signal transduction of vascular smooth muscle for coronary spasm in a porcine model.(4)We have demonstrated that long-term treatment with a Rho-kinase inhibitor suppresses the development of in-stent restenosis in porcine coronary arteries.(5)We have demonstrated that long-term treatment with a Rho-kinase inhibitor suppresses the development of LV remodeling after myocardial infarction in mice through inhibition of the expression of inflammatory cytokines.(6)We have demonstrated that long-term treatment with a Rho-kinase inhibitor suppresses the development of monocrotaline-induced pulmonary hypertension in rats.(7)We have demonstrated that Rho-kinase is substantially mediated in the pathogenesis of microvascular angina.

(1)我们证明Rho/Rho激酶介导的通路在高血压的发病机制中发挥着重要作用。(2)我们证明Rho激酶介导的通路实质上参与了血管紧张素II诱导的心血管疾病的发病机制(3)我们已经证明，在猪模型中，Rho激酶位于血管平滑肌信号转导中的PKC下游，用于冠状动脉痉挛。(4)我们已经证明，长期使用 Rho 激酶抑制剂治疗可抑制猪冠状动脉支架内再狭窄的发展。(5)我们已经证明，长期使用 Rho 激酶抑制剂治疗可抑制猪心肌梗死后左室重构的发展。 (6)我们已经证明，长期使用 Rho 激酶抑制剂治疗可以抑制大鼠野百合碱诱导的肺动脉高压的发展。(7)我们已证明 Rho 激酶在微血管性心绞痛的发病机制中发挥重要作用。

项目成果

Matsumoto Y, ---, Shimokawa H.: "Long-term inhibition of Rho-kinase suppresses Neointimal formation after stent implantation In porcine coronary arteries -Involvement of Multiple mechanisms-"Arteriosclerosis, Thrombosis and Vascular Biology. 24. 181-186 (

Matsumoto Y, ---, Shimokawa H.：“长期抑制 Rho 激酶可抑制猪冠状动脉支架植入后的新内膜形成 - 多种机制的参与 -”动脉硬化、血栓形成和血管生物学。

Shimokawa H: "Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases"Journal of Cardiovascular Pharmacology. (in press). (2002)

Shimokawa H：“Rho激酶作为治疗心血管疾病的新型治疗靶点”心血管药理学杂志。

Matsumoto Y, Shimokawa H: "Long-term inhibition of Rho-kinase suppresses neointimal formation after stent implantation in porcine coronary arteries -Involvement of multiple mechanisms-"Arteriosclerosis, Thrombosis, and Vascular Biology. 24. 181-186 (2003)

Matsumoto Y，Shimokawa H：“长期抑制 Rho 激酶可抑制猪冠状动脉支架植入后的新内膜形成 - 涉及多种机制 -”动脉硬化、血栓形成和血管生物学。

Takemoto M, et al.: "Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase"Circulation. 106. 57-62 (2002)

Takemoto M 等人：“Rho 激酶介导缺氧诱导的内皮一氧化氮合酶下调”循环。

Masumoto A, Mohri M, Shimokawa H, et al.: "Suppression of coronary artery spasm by a Rho-kinase inhibitor fasudil in patients with vasospastic angina"Circulation. 105. 1545-1547 (2002)

Masumoto A、Mohri M、Shimokawa H 等人：“Rho 激酶抑制剂法舒地尔对血管痉挛性心绞痛患者的冠状动脉痉挛的抑制作用”。