Cellular and molecular mechanisms of coronary artery spasm: lessons from animal models
- PMID: 10651199
- DOI: 10.1253/jcj.64.1
Cellular and molecular mechanisms of coronary artery spasm: lessons from animal models
Abstract
Coronary artery spasm plays an important role in the pathogenesis of a wide variety of ischemic heart diseases, especially in the Japanese population. Because coronary artery spasm can be induced by a variety of stimuli with different mechanisms of action, the occurrence of the spasm appears to be due to the local hyperreactivity of the coronary artery rather than to an enhanced stimulation with a single mechanism of action. Several lines of evidence indicate that coronary artery spasm is caused primarily by smooth muscle hypercontraction whereas the contribution of endothelial dysfunction may be minimal. In order to elucidate the cellular and molecular mechanisms of the spasm, porcine models of the spasm were developed. In the first model with balloon injury and high-cholesterol feeding, a close topological correlation between the early atherosclerotic lesions and the spastic sites was noted, whereas in the second model with an inflammatory cytokine the potential importance of coronary inflammatory changes, especially at the adventitia, was noted. Subsequent studies in vivo and in vitro demonstrated that protein kinase C (PKC) and Rho-kinase are substantially involved in the intracellular mechanism of the spasm, resulting in increases in the mono- and diphosphorylations of myosin light chain (MLC). Furthermore, molecular biological analyses demonstrated that Rho-kinase is upregulated at the spastic site (at all levels, including mRNA, protein, and activity), resulting in the inhibition of MLC phosphatase through the phosphorylation of its myosin binding subunit and thereby causing the increase in MLC phosphorylations. Preliminary results also suggest that the long-term inhibition of Rho-kinase is effective in inhibiting the development of arteriosclerotic vascular lesions in several porcine models. Thus, Rho-kinase could be regarded as a novel therapeutic target for coronary arteriosclerosis in general and coronary artery spasm in particular.
Similar articles
-
[Research Progress and Forensic Application on the Pathogenesis of Coronary Artery Spasm].Fa Yi Xue Za Zhi. 2018 Feb;34(1):60-66. doi: 10.3969/j.issn.1004-5619.2018.01.012. Epub 2018 Feb 25. Fa Yi Xue Za Zhi. 2018. PMID: 29577707 Review. Chinese.
-
Endothelial function and coronary spastic angina.Intern Med. 2005 Feb;44(2):91-9. doi: 10.2169/internalmedicine.44.91. Intern Med. 2005. PMID: 15750267 Review.
-
Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1beta.Circulation. 2000 Mar 21;101(11):1319-23. doi: 10.1161/01.cir.101.11.1319. Circulation. 2000. PMID: 10725293
-
Rho-kinase-mediated pathway induces enhanced myosin light chain phosphorylations in a swine model of coronary artery spasm.Cardiovasc Res. 1999 Sep;43(4):1029-39. doi: 10.1016/s0008-6363(99)00144-3. Cardiovasc Res. 1999. PMID: 10615430
-
Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1beta.Circulation. 1997 Dec 16;96(12):4357-63. doi: 10.1161/01.cir.96.12.4357. Circulation. 1997. PMID: 9416904
Cited by
-
Surgical revascularization for severe spasm in the left main coronary artery.Clin Case Rep. 2023 Jan 6;11(1):e6815. doi: 10.1002/ccr3.6815. eCollection 2023 Jan. Clin Case Rep. 2023. PMID: 36619494 Free PMC article.
-
Endothelium-Derived Relaxing Factors and Endothelial Function: A Systematic Review.Biomedicines. 2022 Nov 10;10(11):2884. doi: 10.3390/biomedicines10112884. Biomedicines. 2022. PMID: 36359402 Free PMC article. Review.
-
Cellular Mechanisms of Coronary Artery Spasm.Biomedicines. 2022 Sep 21;10(10):2349. doi: 10.3390/biomedicines10102349. Biomedicines. 2022. PMID: 36289612 Free PMC article. Review.
-
Coronary Artery Spasm: New Insights.J Interv Cardiol. 2020 May 14;2020:5894586. doi: 10.1155/2020/5894586. eCollection 2020. J Interv Cardiol. 2020. PMID: 32508542 Free PMC article. Review.
-
Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques.Pathol Int. 2020 Jun;70(6):309-322. doi: 10.1111/pin.12921. Epub 2020 Mar 13. Pathol Int. 2020. PMID: 32166823 Free PMC article. Review.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources