(Circulation. 1997;96:4357-4363.)
© 1997 American Heart Association, Inc.
Articles |
Enhanced Myosin Light Chain Phosphorylations as a Central Mechanism for Coronary Artery Spasm in a Swine Model With Interleukin-1ß
From the Research Institute of Angiocardiology and Cardiovascular Clinic (N.K., H.S., T.K., T.Y., K.K., A.T.), Kyushu University School of Medicine, Fukuoka 812–82, Japan, and Life Science Center (M.S., I.I., T.A., Y.S.), Asahi Chemical Industry, Co. Ltd., Shizuoka 410–23, Japan.
Correspondence to Hiroaki Shimokawa, MD, PhD, The Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, 3–1-1 Maidashi, Higashi-ku, Fukuoka 812–82, Japan. E-mail shimo{at}cardiol.med.kyushu-u.ac.jp
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-1ß (IL-1ß).
Methods and Results IL-1ß was applied chronically to the porcine coronary arteries from the adventitia to induce an inflammatory/proliferative lesion. Two weeks after the operation, intracoronary serotonin repeatedly induced coronary hyperconstrictions at the IL-1ß-treated site both in vivo and in vitro, which were markedly inhibited by fasudil, an inhibitor of protein kinases, including protein kinase C and MLC kinase. Western blot analysis showed that during serotonin-induced contractions, MLC monophosphorylation was significantly increased and sustained in the spastic segment compared with the control segment, whereas MLC diphosphorylation was noted only in the spastic segment. A significant correlation was noted between the serotonin-induced contractions and MLC phosphorylations. Both types of MLC phosphorylation were markedly inhibited by fasudil. In addition, MLC diphosphorylation was never induced by a simple endothelium removal in the normal coronary artery, whereas enhanced MLC phosphorylations in the spastic segment were noted regardless of the presence or absence of the endothelium.
Conclusions These results indicate that enhanced MLC phosphorylations in the vascular smooth muscle play a central role in the pathogenesis of coronary spasm in our swine model.
Key Words: coronary vasospasm • myosin light chain • calcium • phosphorylation
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