Analysis of the function of endothelial ROCK1 in pulmonary hypertension

我调查分析了ROCK1在血管疾病的调控机制中所起的作用，得到以下结果：1。采用小鼠颈总动脉结扎模型分析ROCK1在血管重构中的作用。与野生型小鼠相比，ROCK1+/-小鼠颈动脉内膜增厚和狭窄减少。与野生型小鼠相比，ROCK1+/-小鼠颈动脉结扎后血管炎症和血管壁细胞DNA合成减少。与ROCK1+/-小鼠相似，野生型小鼠接受ROCK1+/-小鼠骨髓移植后血管重构减少。与野生型小鼠相比，ROCK1+/-小鼠培养的血管内皮细胞显示出ROCK活性降低和粘附分子表达抑制。与野生型小鼠相比，从ROCK1+/-小鼠获得的血管平滑肌细胞显示出ROCK活性降低和细胞迁移抑制。抑制ROCK降低了局灶复合体对局灶黏附和细胞运动的成熟。抑制ROCK刺激BH4的合成，从而增加内皮细胞中一氧化氮的产生。

I investigated to analyze the roles of ROCK1 in regulation mechanism of vascular diseases by ROCK1 and obtained the following results.1. The role of ROCK1 in vascular remodeling was analyzed using mouse common carotid ligation model. Intimal thickening and stenosis in carotid arteries in ROCK1+/- mice were reduced as compared to those in wild-type mice.2. Vascular inflammation and DNA synthesis of vascular wall cells after carotid ligation in ROCK1+/- mice were reduced as compared to those in wild-type mice.3. Similarly to ROCK1+/- mice, reduced vascular remodeling was observed in wild-type mice received bone marrow transplantation of ROCK1+/- mice.4. Vascular endothelial cells primary cultured from ROCK1+/- mice showed reduced ROCK activity and inhibition of adhesion molecule expression as compared to those from wild-type mice.5. Vascular smooth muscle cells obtained from ROCK1+/- mice showed reduced ROCK activity and inhibition of cell migration as compared to those from wild-type mice.6. Inhibition of ROCK reduced maturation of focal complex to focal adhesion and cell movement.7. Inhibition of ROCK stimulated BH4 synthesis and thereby increased nitric oxide production in endothelial cells.