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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115 Citations (Scopus)

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 - Jan 1 1997
Externally publishedYes

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Myosin Light Chains
Spasm
Interleukin-1
Coronary Vessels
Swine
Phosphorylation
Muscle Spasticity
Serotonin
Vascular Smooth Muscle
Endothelium
Myosin-Light-Chain Kinase
Adventitia
Myocardial Ischemia
Western Blotting

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Katsumata, N., Shimokawa, H., Seto, M., Kozai, T., Yamawaki, T., Kuwata, K., ... 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

Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1β. / Katsumata, Naoki; Shimokawa, Hiroaki; Seto, Minoru; Kozai, Toshiyuki; Yamawaki, Tohru; Kuwata, Kouichi; Egashira, Kensuke; Ikegaki, Ichiro; Asano, Toshio; Sasaki, Yasuharu; Takeshita, Akira.

In: Circulation, Vol. 96, No. 12, 01.01.1997, p. 4357-4363.

Research output: Contribution to journalArticle

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, vol. 96, no. 12, pp. 4357-4363. https://doi.org/10.1161/01.CIR.96.12.4357
Katsumata, Naoki ; Shimokawa, Hiroaki ; Seto, Minoru ; Kozai, Toshiyuki ; Yamawaki, Tohru ; Kuwata, Kouichi ; Egashira, Kensuke ; Ikegaki, Ichiro ; Asano, Toshio ; Sasaki, Yasuharu ; Takeshita, Akira. / Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1β. In: Circulation. 1997 ; Vol. 96, No. 12. pp. 4357-4363.
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AU - Kozai, Toshiyuki

AU - Yamawaki, Tohru

AU - Kuwata, Kouichi

AU - Egashira, Kensuke

AU - Ikegaki, Ichiro

AU - Asano, Toshio

AU - Sasaki, Yasuharu

AU - Takeshita, Akira

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