ENHANCED MYOSIN LIGHT-CHAIN PHOSPHORYLATIONS AS A CENTRAL MECHANISM FOR CORONARY-ARTERY SPASM IN A SWINE MODEL WITH INTERLEUKIN-1-BETA

Background Although coronary artery spasm plays an important role in a wide variety of ischemic heart diseases, the intracellular mechanism for the spasm remains to be clarified. We examined the role of myosin light chain (MLC) phosphorylations, a key mechanism for contraction of vascular smooth muscle, in our swine model with interleukin-1 beta (I L-1 beta). Methods and Results IL-1 beta was applied chronically to th e porcine coronary arteries from the adventitia to induce an inflammat ory/proliferative lesion. Two weeks after the operation, intracoronary serotonin repeatedly induced coronary hy perconstrictions at the IL-1 beta-treated site both in vivo and in vitro, which were markedly inhi bited by fasudil, an inhibitor of protein kinases, including protein k inase C and MLC kinase. Western blot analysis showed that during serot onin-induced contractions, MLC monophosphorylation was significantly i ncreased and sustained in the spastic segment compared with the contro l segment, whereas MLC diphosphorylation was noted only in the spastic segment. A significant correlation was noted between the serotonin-in duced contractions and MLC phosphorylations. Both types of MLC phospho rylation were markedly inhibited by fasudil. In addition, MLC diphosph orylation was never induced by a simple endothelium removal in the nor mal coronary artery, whereas enhanced MLC phosphorylations in the spas tic segment were noted regardless of the presence or absence of the en dothelium. Conclusions These results indicate that enhanced MLC phosph orylations in the vascular smooth muscle play a central role in the pa thogenesis of coronary spasm in our swine model.