Inhibition of myosin phosphatase by upregulated Rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1 beta

Article

关键词: VASCULAR SMOOTH-MUSCLE;    PIGS IN-VIVO;    C-MEDIATED PATHWAY;    PROTEIN-KINASE;    LIGHT-CHAIN;    SWINE MODEL;    VASOSPASTIC RESPONSES;    SIGNAL-TRANSDUCTION;    MINIATURE SWINE;    CALYCULIN-A;   

DOI  :  10.1161/01.CIR.101.11.1319

来源: SCIE

【 摘 要 】

Background-We recently demonstrated that the Rho-kinase-mediated pathway plays an important role for coronary artery spasm in our porcine model with interleukin-1 beta (IL-1 beta). In this study, we examined whether or not Rho-kinase is upregulated at the spastic site and if so, how it induces vascular smooth muscle hypercontraction. Methods and Results-Segments of the left porcine coronary artery were chronically treated from the adventitia with IL-1 beta-bound microbeads. Two weeks after the operation, as reported previously, intracoronary serotonin repeatedly induced coronary hypercontractions at the IL-1 beta-treated site both in vivo and in vitro, which were. markedly inhibited by Y-27632, one of the specific inhibitors of Rho-kinase, Reverse transcription-polymerase chain reaction analysis demonstrated that the expression of Rho-kinase mRNA was significantly increased in the spastic compared with the control segment. Western blot analysis showed that during the serotonin-induced contractions, the extent of phosphorylation of the myosin-binding subunit of myosin phosphatase (MBS), one of the major substrates of Rho-kinase, was significantly greater in the spastic than in the control segment and that the increase in MBS phosphorylations was also markedly inhibited by Y-27632. There was a highly significant correlation between the extent of MBS phosphorylations and that of contractions. Conclusions-These results indicate that Rho-kinase is upregulated at the spastic site and plays a key role in inducing vascular smooth muscle hypercontraction by inhibiting myosin phosphatase through the phosphorylation of MBS in our porcine model.

【 授权许可】

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