Abstract
Despite considerable research effort, the pathogenesis of coronary vasospasm has not yet been fully elucidated. In this chapter we review the general hypothesis of vasospastic coronary artery behavior, present the current experimental models, and discuss potential clinical applications.
Similar content being viewed by others
Abbreviations
- Coronary vasospasm:
-
State of functional hemodynamically relevant narrowing of a coronary artery due to hypercontraction of smooth muscle cells of the coronary artery walls.
References
Alessi D, MacDougall LK, Sola MM, Ikebe M, Cohen P (1992) The control of protein phosphatase-1 by targeting subunits. The major myosin phosphatase in avian smooth muscle is a novel form of protein phosphatase-1. Eur J Biochem 210:1023–1035
Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T et al (1996) Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem 271:20246–20249
Amano M, Chihara K, Nakamura N, Fukata Y, Yano T, Shibata M et al (1998) Myosin II activation promotes neurite retraction during the action of Rho and Rho-kinase. Genes Cells 3:177–188
Beltrame JF, Sasayama S, Maseri A (1999) Racial heterogeneity in coronary artery vasomotor reactivity: differences between Japanese and Caucasian patients. J Am Coll Cardiol 33:1442–1452
Berrige MJ (1993) Inositol triphosphate and calcium signaling. Nature 361:315–325
Butler WE, Peterson JW, Zervas NT, Morgan KG (1996) Intracellular calcium, myosin light chain phosphorylation, and contractile force in experimental cerebral vasospasm. Neurosurgery 38:781–788
Campbell GR, Campbell JH (1985) Recent advances in molecular pathology: smooth muscle phenotypic changes in arterial wall homeostasis implications for atherosclerosis. Exp Mol Pathol 42:139–162
Chen YH, Chen MX, Alessi DR, Campbell DG, Shanahan C, Cohen P et al (1994) Molecular cloning of cDNA encoding the 110-kDa and 21-kDa regulatory subunits of smooth muscle protein phosphatase 1M. FEBS Lett 356:51–55
Chihara K, Amano M, Nakamura N, Yano T, Shibata M, Tokui T et al (1997) Cytoskeletal rearrangements and transcriptional activation of c-fos serum response element by Rho-kinase. J Biol Chem 272:25121–25127
Dinarello CA (1988) Biology of interleukin 1. FASEB J 2:108–115
Egashira K, Inou T, Yamada A, Hirooka Y, Takeshita A (1992) Preserved endothelium- dependent vasodilation at the vasospastic site in patients with variant angina. J Clin Invest 89:1047–1052
Eto M, Ohmori T, Suzuki M, Furuya K, Morita F (1995) A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C: isolation from porcine aorta media and characterization. J Biochem 118:1104–1107
Eto Y, Shimokawa H, Hiroaki J, Morishige K, Kandabashi T, Matsumoto Y et al (2000) Gene transfer of dominant negative Rho kinase suppresses neointimal formation after balloon injury. Am J Physiol 278:H1744–H1750
Forman MB, Oates JA, Robertson D, Robertson RM, Roberts LJ, Virmani R (1985) Increased adventitial mast cells in a patient with coronary spasm. N Engl J Med 313:1138–1141
Fukumoto Y, Shimokawa H, Kozai T, Kadokami Y, Kuwata K, Owada MK et al (1996) Tyrosine kinase inhibitor suppresses the (re)stenotic changes of the coronary artery after balloon injury in pigs. Cardiovasc Res 32:1131–1140
Fukumoto Y, Shimokawa H, Ito A, Kadokami T, Yonemitsu Y, Aikawa M et al (1997a) Inflammatory cytokines cause coronary arteriosclerosis-like changes and alterations in the smooth muscle phenotypes in pigs. J Cardiovasc Pharmacol 29:222–231
Fukumoto Y, Shimokawa H, Kozai T, Kadokami T, Kuwata K, Yonemitsu Y et al (1997b) Vasculoprotective role of inducible nitric oxide synthase at inflammatory coronary lesions induced by chronic treatment with interleukin-1β in pigs in vivo. Circulation 96:3104–3111
Fuster V, Badimon L, Badimon JJ, Chesebro JH (1992) The pathogenesis of coronary artery disease and the acute coronary syndromes II. N Engl J Med 326:310–318
Gong MC, Iizuka K, Nixon G, Browne JP, Hall A, Eccleston JF et al (1996) Role of guanosine nucleotide-binding proteins-ras family or trimeric proteins or both in Ca2+ sensitization of smooth muscle. Proc Natl Acad Sci USA 93:1340–1345
Hannson GK, Jonasson L, Seifert PS, Stemme S (1989) Immune mechanism in atherosclerosis. Arteriosclerosis 9:567–578
Hirata K, Kikuchi A, Sasaki T, Kuroda S, Kaibuchi K, Matsuura Y et al (1992) Involvement of Rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle contraction. J Biol Chem 267:8719–8722
Ikebe M, Brozovich FV (1996) Protein kinase C increases force and slows relaxation in smooth muscle: evidence for regulation of the myosin light chain phosphatase. Biochem Biophys Res Commun 225:370–376
Ikebe M, Hartshorne DJ (1985) Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase. J Biol Chem 260:10027–10031
Ito A, Shimokawa H, Nakaike R, Fukai T, Sakata M, Takayanagi T et al (1994) Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm. Circulation 90:2425–2431
Ito A, Shimokawa H, Kadokami T, Fukumoto Y, Owada MK, Shiraishi T et al (1995) Tyrosine kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced by chronic treatment with interleukin-1β in pigs in vivo. J Clin Invest 96:1288–1294
Ito A, Shimokawa H, Fukumoto Y, Kadokami T, Nakaike R, Takayanagi T et al (1996) The role of fibroblast growth factor-2 in the vascular effects of interleukin-1β in porcine coronary arteries in vivo. Cardiovasc Res 32:570–579
Jougasaki M, Yasue H, Takahashi K (1989) Perivascular nerve lesion of the coronary artery involved in spasm in a patient with variant angina. Pathology 21:304–307
Kadokami T, Shimokawa H, Fukumoto Y, Ito A, Takayanagi T, Egashira K et al (1996) Coronary artery spasm does not depend on the intracellular calcium store but is substantially mediated by the protein kinase C-mediated pathway in a swine model with interleukin-1β. Circulation 94:190–196
Kamm KE, Stull JT (1989) Regulation of smooth muscle contractile elements by second messengers. Annu Rev Physiol 51:299–318
Kanazawa K, Suematsu M, Ishida T, Hirata K, Kawashima S, Akita H et al (1997) Disparity between serotonin- and acetylcholine-provoked coronary artery spasm. Clin Cardiol 20:146–152
Kandabashi T, Shimokawa H, Miyata K, Kunihiro I, Kawano Y, Fukata Y et al (2000) Inhibition of myosin phosphatase by up-regulated Rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1β. Circulation 101:1319–1323
Katsumata N, Shimokawa H, Seto M, Kozai T, Yamawaki T, Kuwata K et al (1997) Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1β. Circulation 96:4357–4363
Kimura K, Ito M, Amano M, Chihara K, Fukata Y, Nakafuku M et al (1996) Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 273:245–248
Kitazawa T, Masuo M, Somlyo AP (1991) G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc Natl Acad Sci USA 88:9307–9310
Kohchi KS, Takebayashi S, Hiroki T, Nobuyoshi M (1985) Significance of adventitial inflammation of the coronary artery in patients with unstable angina: results at autopsy. Circulation 71:709–716
Kozai T, Shimokawa H, Yamawaki T, Fukumoto Y, Kadokami T, Kuwata K et al (1997a) Platelet activating factor causes hyperconstriction at the inflammatory coronary lesions in pigs in vivo. Coronary Art Dis 8:423–432
Kozai T, Shimokawa H, Fukumoto Y, Kobayashi S, Owada MK, Kadokami T et al (1997b) Tyrosine kinase inhibitor markedly suppresses the development of coronary lesions induced by chronic treatment with platelet-derived growth factor in pigs in vivo. J Cardiovasc Pharmacol 29:536–545
Kuga T, Tagawa H, Tomoike H, Mitsuoka W, Egashira S, Ohara Y et al (1993) Role of coronary artery spasm in progression of organic stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm. Circulation 87:573–582
Kuga T, Egashira K, Mohri M, Tsutsui H, Harasawa Y, Urabe Y (1995) Bradykinin-induced vasodilation is impaired at the atherosclerotic site but is preserved at the spastic site of human coronary arteries in vivo. Circulation 92:183–189
Kuga T, Shimokawa H, Hirakawa Y, Kadokami T, Arai Y, Fukumoto Y et al (2000) Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm. J Cardiovasc Pharmacol 35:822–828
Kureishi Y, Kobayashi S, Amano M, Kimura K, Kanaide H, Nakano T et al (1997) Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation. J Biol Chem 272:12257–12260
Lange RA, Cigarroa RG, Yancy CW Jr, Willard JE, Pompa JJ, Sills MN et al (1989) Cocaine-induced coronary artery vasoconstriction. N Engl J Med 321:1557–1562
Mark DB, Califf RM, Morris KG, Harrell FE, Pryor DB, Hlatky MA et al (1984) Clinical characteristics and long-term survival of patients with variant angina. Circulation 69:880–888
Maseri A, Severi S, Nes MD, L'Abbate A, Chierchia S, Marzilli M et al (1978) “Variant” angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia: pathogenetic mechanisms, estimated incidence and clinical and coronary angiographic findings in 138 patients. Am J Cardiol 42:1019–1035
Maseri A, Davies G, Hackett D, Kaski JC (1990) Coronary artery spasm and vasoconstriction. The case for a distinction. Circulation 81:1983–1991
Masumoto A, Mohri M, Shimokawa H, Urakami L, Usui M, Takeshita A (2002) Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina. Circulation 105:1545–1547
McFadden EP, Bauters C, Lablanche J-M, Quandalle P, Leroy F, Bertland ME (1993) Response of human coronary arteries to serotonin after injury by coronary angioplasty. Circulation 88:2076–2085
Miwa Y, Hirata K, Matsuda Y, Suematsu M, Kawashima S, Yokoyama M (1994) Augmented receptor-mediated Ca2+ mobilization causes supersensitivity of contractile response to serotonin in atherosclerotic arteries. Circ Res 75:1096–1102
Miyata K, Shimokawa H, Yamawaki T, Kunihiro I, Zhou X, Higo T et al (1999) Endothelial vasodilator function is preserved at the spastic/inflammatory coronary lesions in pigs. Circulation 100:1432–1437
Miyata K, Shimokawa H, Higo T, Yamawaki T, Katsumata N, Kandabashi T et al (2000) Sarpogrelate, a selective 5-HT2A serotonergic receptor antagonist, inhibits serotonin-induced coronary artery spasm in a porcine model. J Cardiovasc Pharmacol 35:294–301
Mohri M, Shimokawa H, Hirakawa Y, Masumoto A, Takeshita A (2003) Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm. J Am Coll Cardiol 41:15–19
Morishige K, Shimokawa H, Yamawaki T, Miyata K, Eto Y, kandabashi T, Yogo K, Higo T, Egashira K, Ueno H, Takeshita A (2000) Local adenovirus-mediated transfer of C-type natriuretic peptide suppresses vascular remodeling in porcine coronary arteries in vivo. J Am Coll Cardiol 35:1040–1047
Moyer CF, Sajuthi D, Tulli H, Williams JK (1991) Synthesis of IL-1α and IL-1β by arterial cells in atherosclerosis. Am J Pathol 138:951–960
Murphy RA (1994) What is special about smooth muscle? The significance of covalent cross bridge regulation. FASEB J 38:781–788
Nagasawa K, Tomoike H, Hayashi Y, Yamada A, Yamamoto T, Nakamura M (1989) Intramural hemorrhage and endothelial changes in atherosclerotic coronary artery after repetitive episodes of spasm in X-ray-irradiated hypercholesterolemic pigs. Circ Res 65:272–282
Nakamura M (1991) Experimental induction of spasm, sudden progression of organic stenosis and intramural hemorrhage in the epicardial coronary arteries. Basic Res Cardiol 86:159–172
Nakamura M, Takeshita A, Nose Y (1987) Clinical characteristics associated with myocardial infarction, arrhythmias, and sudden death in patients with vasospastic angina. Circulation 75:1110–1116
Noda M, Fukazawa C, Moriishi K, Kato T, Okuda T, Kurokawa K et al (1995) Involvement of rho in GTP-γS-induced enhancement of phosphorylation of 20-kDa myosin light chain vascular smooth muscle cells: inhibition of phosphatase activity. FEBS Lett 367:246–250
Okumura K, Yasue H, Ishizaka H, Ogawa H, Fujii H, Yoshimura M (1992) Endothelium- dependent dilator response to substance P in patients with coronary spastic angina. J Am Coll Cardiol 20:838–844
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809
Satoh S, Tomoike H, Mitsuoka W, Egashira S, Tagawa H, Kuga T et al (1990) Smooth muscles from spastic coronary artery segment show hyperreactivity to histamine. Am J Physiol 259:H9–H13
Seto M, Sasaki Y, Sasaki Y (1990) Stimulus-specific patterns of myosin light chain phosphorylation in smooth muscle of rabbit thoracic artery. Eur J Physiol 415:484–489
Seto M, Yano K, Sasaki Y, Azuma H (1993) Intimal hyperplasia enhances myosin phosphorylation in rabbit carotid artery. Exp Mol Pathol 58:1–13
Seto M, Sakurada K, Kamm KE, Stull JT, Sasaki Y (1996) Myosin light chain diphosphorylation is enhanced by growth promotion of cultured smooth muscle cells. Eur J Physiol 432:7–13
Severi S, Davies G, Maseri A, Marzullo P, L'Abbate A (1980) Long-term prognosis of “variant” angina with medical treatment. Am J Cardiol 46:226–232
Shimizu H, Ito M, Miyahata M, Ichikawa K, Okubo S, Konishi T et al (1994) Characterization of the myosin-binding subunit of smooth muscle myosin phosphatase. J Biol Chem 269:30407–30411
Shimokawa H (1999) Primary endothelial dysfunction: atherosclerosis. J Mol Cell Cardiol 31:23–37
Shimokawa H (2000) Cellular and molecular mechanisms of coronary artery spasm. Lessons from animal models. Jpn Circ J 64:1–12
Shimokawa H, Takeshita A (1995) Endothelium-dependent regulation of the cardiovascular system. Intern Med 34:939–946
Shimokawa H, Takeshita A (2005) Rho-kinase is an important therapeutic target in cardiovascular medicine. Arterioscler Thromb Vasc Biol 25:1767–1775
Shimokawa H, Vanhoutte PM (1989a) Hypercholesterolemia causes generalized impairment of endothelium-dependent relaxation to aggregating platelets in porcine coronary arteries. J Am Coll Cardiol 13:1402–1408
Shimokawa H, Vanhoutte PM (1989b) Dietary cod-liver oil improves endothelium-dependent relaxations in hypercholesterolemic and atherosclerotic porcine coronary arteries. Circulation 78:1421–1430
Shimokawa H, Tomoike H, Nabeyama S, Yamamoto H, Araki H, Nakamura M et al (1983) Coronary artery spasm induced in atherosclerotic miniature swine. Science 221:560–562
Shimokawa H, Tomoike H, Nabeyama S, Yamamoto H, Ishii Y, Tanaka K et al (1985) Coronary artery spasm induced in miniature swine: angiographic evidence and relation to coronary atherosclerosis. Am Heart J 110:300–310
Shimokawa H, Aarhus LL, Vanhoutte PM (1987) Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin. Circ Res 61:256–270
Shimokawa H, Nagasawa K, Irie T, Egashira S, Egashira K, Sagara T (1988) Clinical characteristics and long-term prognosis of patients with variant angina. A comparative study between western and Japanese populations. Int J Cardiol 18:331–349
Shimokawa H, Lam JYT, Chesebro JH, Bowie EJW, Vanhoutte PM (1989a) Effects of dietary supplementation with cod-liver oil on endothelium-dependent responses in porcine coronary arteries. Circulation 76:898–905
Shimokawa H, Flavahan NA, Shepherd JT, Vanhoutte PM (1989b) Endothelium-dependent inhibition of ergonovine-induced contraction is impaired in porcine coronary arteries with regenerated endothelium. Circulation 80:643–650
Shimokawa H, Flavahan NA, Vanhoutte PM (1989c) Natural course of the impairment of endothelium-dependent relaxation after balloon endothelium removal in porcine coronary arteries: possible dysfunction of a pertussis toxin-sensitive G-protein. Circ Res 65:740–753
Shimokawa H, Ito A, Fukumoto Y, Kadokami T, Nakaike R, Sakata M et al (1996) Chronic treatment with interleukin-1β induces coronary intimal lesions and vasospastic responses in pigs in vivo. The role of platelet-derived growth factor. J Clin Invest 97:769–776
Shimokawa H, Seto M, Katsumata N, Amano M, Kozai T, Yamawaki T et al (1999) Rho-kinase-mediated pathway induces enhanced myosin light chain phosphorylations in a swine model of coronary artery spasm. Cardiovasc Res 43:1029–1039
Shimokawa H, Hiramori K, Iinuma H, Hosoda S, Kishida H, Osada H, Katagiri T, Yamauchi K, Yui Y, Minamino T, Nakashima M, Kato K (2002) Antianginal effect of fasudil, a Rho-kinase inhibitor, in patients with stable effort angina: a multicenter study. J Cardiovasc Pharmacol 40:751–761
Shiroto T, Yasuda S, Tsuburaya R, Ito Y, Takahashi J, Ito K, Ishibashi-Ueda H, Shimokawa H (2009) Role of Rho-kinase in the pathogenesis of coronary hyperconstricting responses induced by drug-eluting stents in pigs in vivo. J Am Coll Cardiol 54:2321–2329
Somlyo AP, Somlyo AV (1994) Signal transduction and regulation in smooth muscle. Nature 372:231–236
Suzuki Y, Tokunaga S, Ikeguchi S, Miki S, Iwase T, Tomita T et al (1992) Induction of coronary artery spasm by intracoronary acetylcholine: comparison with intracoronary ergonovine. Am Heart J 124:39–47
Takemoto M, Sun J, Hiroki J, Shimokawa H, Liao JK (2002) Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase. Circulation 106:57–62
Tashiro H, Shimokawa H, Koyanagi S, Takeshita A (1993) Clinical characteristics of patients with spontaneous remission of variant angina. Jpn Circ J 57:117–122
Tsuburaya R, Yasuda S, Shiroto T, Ito Y, Gao JY, Aizawa K, Kikuchi Y, Ito K, Takahashi J, Ishibashi-Ueda H, Shimokawa H (2012) Long-term treatment with nifedipine suppresses coronary hyperconstricting responses and inflammatory changes induced by paclitaxel-eluting stent in pigs in vivo: possible involvement of Rho-kinase pathway. Eur Heart J 33:791–799
Uehara M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T et al (1997) Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389:990–994
Vanhoutte PM, Shimokawa H (1989) Endothelium-derived relaxing factor(s) and coronary vasospasm. Circulation 80:1–9
Vicari RM, Chaitman B, Keefe D, Smith WB, Chrysant SG, Tonkon MJ, Bittar N, Weiss RJ, Morales-Ballejo H, Thadani U, Fasudil Study Group (2005) Efficacy and safety of fasudil in patients with stable angina: a double-blind, placebo-controlled, phase 2 trial. J Am Coll Cardiol 46:1803–1811
Waters DD, Miller DD, Szlachcic J, Bouchard A, Méthé M, Kreeft J et al (1983) Factors influencing the long-term prognosis of treated patients with variant angina. Circulation 68:258–265
Yamamoto Y, Tomoike H, Egashira K, Nakamura M (1987) Attenuation of endothelium-related relaxation and enhanced responsiveness of vascular smooth muscle to histamine in spastic coronary arterial segments from miniature pigs. Circ Res 61:772–778
Yamamoto H, Yoshimura H, Noma M, Kai H, Suzuki S, Tajimi T et al (1992) Preservation of endothelium-dependent vasodilation in the spastic segment of the human epicardial coronary artery by substance P. Am Heart J 123:298–303
Yamamoto H, Yoshimura H, Noma M, Suzuki S, Kai H, Tajimi T et al (1995) Improvement of coronary vasomotion with eicosapentaenoic acid does not inhibit acetylcholine-induced coronary vasospasm in patients with variant angina. Jpn Circ J 59:608–616
Yasue H, Omote S, Takizawa A, Nagao M (1983) Coronary arterial spasm in ischemic heart disease and its pathogenesis. A review. Circ Res 52:1147–1152
Yasue H, Takizawa A, Nagao M, Nishida S, Horie M, Kubota J et al (1988) Long-term prognosis for patients with variant angina and influential factors. Circulation 78:1–9
Yogo K, Shimokawa H, Kandabashi T, Miyata K, Okamoto S, Egashira K, Huang PL, Akaike T, Takeshita A (2000) Different vasculoprotective roles of nitric oxide synthase isoforms in the vascular lesion formation in mice. Arterioscler Thromb Vasc Biol 20:e96–e100
Yokoyama M, Akita H, Hirata K, Usuki S, Fukuzaki H, Itoh H (1990) Supersensitivity of isolated coronary artery to ergonovine in a patient with variant angina. Am J Med 89:507–515
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Shimokawa, H. (2014). Coronary Artery Spasm, Part II Basic Aspects. In: Lanzer, P. (eds) PanVascular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37393-0_59-1
Download citation
DOI: https://doi.org/10.1007/978-3-642-37393-0_59-1
Received:
Accepted:
Published:
Publisher Name: Springer, Berlin, Heidelberg
Online ISBN: 978-3-642-37393-0
eBook Packages: Springer Reference MedicineReference Module Medicine