(Circulation. 1995;92:1083.)
© 1995 American Heart Association, Inc.
Articles |
Infiltrates of Activated Mast Cells at the Site of Coronary Atheromatous Erosion or Rupture in Myocardial Infarction
Correspondence to Paris Constantinides, MD, PhD, 430 Chester Rd, Qualicum Beach, BC, V9K 1B9, Canada.
Key Words: Editorials • cells • atherosclerosis • plaque • thrombus
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Introduction |
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 Top Introduction References |
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In the early 1960s, complete serial section studies through the whole thrombosed segment of occluded coronary arteries of myocardial infarction patients autopsied in St Louis, Mo, showed that all of the occluding thrombi had been caused by fissures of the surface of the underlying atherosclerotic plaques, fissures through which blood sometimes entered the plaque interior before they were sealed by the thrombi.1 Because essentially similar findings have since been made in Germany,2 Great Britain,3 Denmark,4 and Russia (A. Vichert, personal communication, 1985) and the same scenario was found to be responsible for cerebral artery thrombosis,5 it now seems certain that thrombosis in human atherosclerotic arteries is always triggered by a disruption of their plaque surfaces, even though the size the thrombi achieve and how long they persist probably depends on systemic factors that prevailed at the time of the disruption. In other words, plaque disruptions may occur all the time, but in some persons with high blood coagulability and/or low plasma fibrinolysin activity, they may cause large occlusive thrombi and myocardial infarction, whereas in others they may produce only small nonocclusive thrombi without myocardial necrosis.
Unfortunately, the processes that induce plaque disruption are still unknown. They could be physical stresses or chemical insults emanating from the blood or the plaque interior, insults that disrupt the plaque directly or increase its vulnerability to other factors.
Among the disrupting agents generally considered possible so far are (1) endothelium-injuring processes, (2) factors that damage or kill the myocytes that produce and maintain the collagenic cap of atheromata, (3) oxidases or peroxides released by subendothelial macrophages that could cross-link the polypeptide chains of the cap collagen and make the latter stiffer and more brittle than normal, (4) degradation products from the atheroma lipid pool itself, (5) circulating immune complexes that could penetrate into plaques and activate complement, and (6) autoimmune attacks against some plaque components because they may appear antigenically different from normal arterial wall constituents and therefore "foreign" to the immune system.
The elegant article by Kovanen et al6 that appears in the current issue of Circulation is the first to point to a completely novel possible plaque-disrupting factor, ie, the release of collagen-degrading proteases from mast cells in the plaque.
Circulating mast cell precursors could well penetrate selectively into the atheromata, because it has been shown ultrastructurally that the junctions between endothelial cells that line human plaques are often open, in contrast to junctions over the normal arterial wall, which are usually closed.8
Since some antibodies attached to mast cells can trigger the release of mast cell contents whenever they encounter and bind the antigens that elicited their generation, this article also raises the theoretical possibility that even ordinary allergic reactions could promote plaque disruption.
Evidently, additional morphometric studies of subthrombic plaque histology in autopsies of persons who die of myocardial infarction, such as the study by Kovanen et al, will be needed to uncover the entire spectrum of local parameter changes that can promote plaque disruption. It may well turn out that different scenarios can cause plaque disruption in different persons.
After consensus is reached on the spectrum of possible plaque-disrupting processes visible at the autopsy level, the time will come to try to identify living persons at risk for plaque disruption.
Fortunately, procedures for plaque protection and prevention of disruption could be developed in currently available atherosclerotic animal models in which disruption and arterial thrombosis can be triggered at will.7
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References |
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TopIntroductionReferences |
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1. Constantinides P. Coronary thrombosis linked to fissures in atherosclerotic vessel wall. JAMA. 1964;188:35-36.
2. Sinapins D. Über Wandveränderungen bei Coronar-Thrombose. Klin Wochenschr. 1965;43:875-880. [Medline] [Order article via Infotrieve]
3. Davies MJ, Thomas A. The pathological basis and microanatomy of occlusive thrombus formation in human coronary arteries. Philos Trans R Soc Lond Biol. 1981;294:225-229. [Medline] [Order article via Infotrieve]
4.
Falk E. Plaque rupture with severe
pre-existing stenosis precipitating coronary
thrombosis. Br Heart J. 1983;50:127-134.
5. Constantinides P. Pathogenesis of cerebral artery thrombosis in man. Arch Pathol. 1967;83:422-428. [Medline] [Order article via Infotrieve]
6.
Kovanen PT, Kaartinen M, Paavonen T.
Infiltrates of activated mast cells at the site of
coronary atheromatous erosion or rupture in
myocardial infarction. Circulation. 1995;92:1084-1088.
7.
Abela GS, Picon PD, Friedl SE, Gebara OC, Miyamoto A,
Federman M, Tofler GH, Muller JE. Triggering of plaque
disruption and arterial thrombosis in an atherosclerotic
rabbit model. Circulation. 1995;91:776-784.
8. Constantinides P, Harkey M. Electron microscopic exploration of human endothelium in early and advanced atherosclerotic lesions. Ann N Y Acad Sci. 1990;598:113-124. [Medline] [Order article via Infotrieve]
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