Experimental and Clinical Studies on the Role of Inflammatory Mechanisms in the Pathogenesis of Ischemic Heart Disease

点击翻译按钮获取中文摘要

(Experimental studies)1. The long-term adventitial treatment with IL-1βresulted in the development of vascular remodeling and neointimal formation of the porcine coronary artery in vivo, whereas endothelial vasodilator functions were fairly preserved.2. In this porcine model, inducible NO synthase (iNOS) was transiently expressed in VSMC and exerted an inhibitory effect against vascular lesion formation in vivo.3. Regarding the molecular mechanism of the coronary artery spasm in this porcine model, it was shown that Rho-kinase is upregulated and inhibits myosin phosphatase, resulting in the increased myosin phosphorylations and hypercontractions of VSMC.4. We have established the method of in vivo gene transfer into the coronary artery in vivo using the infiltrator balloon angioplasty catheter (IABC). Using this novel method, we were able to inhibit the neointimal formation after balloon injury in porcine coronary arteries by overexpressing CNP in vivo.5. The long-term inhibitation of Rho-kinase by either hydroxyfasudil (a specific inhibitor of Rho-kinase) or in vivo gene transfer of dominant negative Rho-kinase resulted in the regression of vascular remodeling caused by inflammatory cytokines.(Clinical studies)In patients with coronary artery disease, the plasma levels of macrophage-colony stimulating factor (M-CSF) were increased while those of transforming factor-b (TGF-b) were decreased, thus stimulating the process of atherosclerosis.