Development of intracellular therapy to induce a regression of coronary arteriosclerotic lesions

1.在球囊损伤的猪股动脉中，Rho激酶在mRNA和活性水平上均上调。显性负性Rho激酶（DNRhoK）的体内基因转移能显著抑制球囊损伤所致血管病变的发展.用MCP-1和Ox-LDL从外膜长期处理猪冠状动脉引起动脉病变（内膜增厚和几何重塑）的发展。长期应用羟基法舒地尔阻断Rho激酶可显著抑制血管病变的发展.用IL-1β从外膜长期处理猪冠状动脉导致动脉病变（内膜增厚和几何重塑）的发展。用羟基法舒地尔长期阻断Rho激酶可使体内血管病变消退. DNRhoK的体内基因转移可诱导猪IL-1b模型的缩窄性重塑消退。这些结果表明Rho激酶在冠状动脉粥样硬化的发病中起重要作用，长期抑制该分子可诱导动脉粥样硬化血管病变消退。

1. In the porcine femoral arteries injured by balloon technique, Rho-kinase was upregulated both at the mRNA and activity levels. The in vivo gene transfer of dominant-negative Rho-kinase (DNRhoK) significantly inhibited the development of the balloon injury-induced vascular lesions.2. The long-term treatment of the porcine coronary artery from the adventitial with MCP-1 and Ox-LDL caused a development of arteriosclerotic lesions (intimal thickening and geometric remodeling). The long-term blockade of Rho-kinase with hydroxyfasudil significantly suppressed the development of those vascular lesions.3. The long-term treatment of the porcine coronary artery from the adventitial with IL-1β caused a development of arteriosclerotic lesions (intimal thickening and geometric remodeling). The long-term blockade of Rho-kinase with hydroxy fasudil caused a regression of those vascular lesions in vivo.4. The in vivo gene transfer of DNRhoK induced a regression of constrictive remo deling in a porcine model with IL-1b/These results indicate that Rho-kinase is substantially involved in the pathog enesis of coronary arteriosclerosis and that the long-term inhibition of the molecule could induce a regression of the arterioclerotic vascular lesions.