Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1β

Naoki Katsumata, Hiroaki Shimokawa, Minoru Seto, Toshiyuki Kozai, Tohru Yamawaki, Kouichi Kuwata, Kensuke Egashira, Ichiro Ikegaki, Toshio Asano, Yasuharu Sasaki, Akira Takeshita

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Abstract

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-1β (IL-1β). Methods and Results: IL-1β 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-1β-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.

Original languageEnglish
Pages (from-to)4357-4363
Number of pages7
JournalCirculation
Volume96
Issue number12
DOIs
Publication statusPublished - 1997

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Katsumata, N., Shimokawa, H., Seto, M., Kozai, T., Yamawaki, T., Kuwata, K., Egashira, K., Ikegaki, I., Asano, T., Sasaki, Y., & Takeshita, A. (1997). Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1β. Circulation, 96(12), 4357-4363. https://doi.org/10.1161/01.CIR.96.12.4357