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

1)Rho激酶实质上参与动脉硬化的炎症机制。Rho激酶在血管平滑肌细胞中的表达受炎症刺激物如血管紧张素II和IL-1β的上调，并涉及NF-κ B。2）Rho激酶介导缺氧诱导的培养的人内皮细胞中内皮型一氧化氮合酶（eNOS）的下调。Rho激酶特异性抑制剂羟基法舒地尔（Hydroxyfasudil）可预防缺氧诱导的eNOS下调。3）长期抑制Rho激酶可抑制猪冠状动脉支架内再狭窄，其机制涉及多个方面，包括促进VSMC凋亡、抑制MCP-1表达和抑制炎性细胞募集。和通过TGF-β 1抑制抑制胶原合成。4）Rho-激酶的长期抑制通过多种机制抑制血管紧张素II诱导的心血管损伤的形成，包括抑制NAD（P）H和TGF-β1的表达以及超氧化物的产生。5）Rho激酶的长期抑制抑制心脏移植物血管病变，其中涉及抑制巨噬细胞移动抑制因子（MIF）的表达。

1) Rho-kinase is substantially involved in the inflammatory mechanisms of arteriosclerosis. The expression of Rho-kinase in vascular smooth muscle cells is upregulated by inflammatory stimuli, such as angiotensin II and IL-1β with an involvement of Nf-_KB.2) Rho-kinase mediates hypoxia-induced downregulation of endothelial NO synthase (eNOS) in cultured human endothelial cells. Hydroxyfasudil, a specific Rho-kinase inhibitor, prevents the hypoxia-induced downregufayion of eNOS.3) Long-term inhibition of Rho-kinase suppresses in-stent restenosis in porcine coronary arteries, in which multiple mechanisms are involved, including enhancement of VSMC apoptosis, suppression of MCP-1 expression and inflammatory cell recruitment, and suppression of collagen synthesis through TGF-bl inhibition.4) Long-term inhibition of Rho-kinase suppresses angiotensin Il-induced formation of cardiovascular lesions by multiple mechanisms, including suppressions of NAD(P)H and TGF-β1 expression and of superoxide production.5) Long-term inhibition of Rho-kinase suppresses cardiac allograft vasculopathy, in which inhibition of the expression of macrophage migration inhibitory factor (MIF) is involved.