Analysis of the function of endothelial ROCK1 in pulmonary hypertension

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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.