Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction

Arbustini, Eloisa; Bello, Barbara Dal; Morbini, Patrizia; Burke, Allen; Bocciarelli, M; Specchia, Giuśeppe; Virmani, Renu

doi:10.1136/hrt.82.3.269

Cited by 418 publications

(228 citation statements)

References 15 publications

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“…The presence of TG in the fibrous cap and at the shoulder regions of atherosclerotic plaques could be effective in stabilizing the artery at these sites, rendering it less prone to rupture. The presence of transglutaminase on the luminal endothelium may prevent the dislodgment or erosion of endothelial cells that leads to coronary thrombosis without anatomical evidence of plaque rupture (Arbustini et al, 1999;Davies, 1997). The microvascular endothelial transglutaminase, on the other hand, could prevent the increased permeability and intra-plaque hemorrhage that often accompanies these vessels and that may predispose them to plaque rupture (Barger and Beeuwkes, 1990;McCarthy et al, 1999;Paterson, 1938;Zhang et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Localization of Tissue Transglutaminase in Human Carotid and Coronary Artery Atherosclerosis: Implications for Plaque Stability and Progression

Haroon

Wannenburg

Gupta

et al. 2001

Laboratory Investigation

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SUMMARY:Although atherosclerosis progresses in an indolent state for decades, the rupture of plaques creates acute ischemic syndromes that may culminate in myocardial infarction and stroke. Mechanical forces and matrix metalloproteinase activity initiate plaque rupture, whereas tissue inhibitors of metalloproteinases have an important (albeit indirect) role in plaque stabilization. In this paper, an enzyme that could directly stabilize the plaque is described. Tissue transglutaminase (TG) catalyzes the formation of ⑀(␥-glutamyl)lysine isopeptide bonds that are resistant to enzymatic, mechanical, and chemical degradation. We performed immunohistochemistry for TG in atherosclerotic human coronary and carotid arteries. TG was most prominent along the luminal endothelium and in the medium of the vessels with a distribution mirroring that of smooth muscle cells. Variable, often prominent, immunoreactivity for TG was also seen in the intima, especially in regions with significant neovascularization. Additionally, TG was detected in fibrous caps and near the "shoulder regions" of some plaques. A monoclonal antibody to the transglutaminase product ⑀(␥-glutamyl)lysine isopeptide demonstrated co-localization with TG antigen. Transglutaminase activity was found in 6 of 14 coronary artery atherectomy samples. Cross-linking of TG substrates such as fibrinogen, fibronectin, vitronectin, collagen type I, and protease inhibitors stabilized the plaque. Furthermore, the activation of transforming growth factor-beta-1 by TG might be an additional mechanism for the promotion of plaque stabilization and progression by increasing the synthesis of extracellular matrix components. (Lab Invest 2001, 81:83-93).

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Section: Discussionmentioning

confidence: 99%

Localization of Tissue Transglutaminase in Human Carotid and Coronary Artery Atherosclerosis: Implications for Plaque Stability and Progression

Haroon

Wannenburg

Gupta

et al. 2001

Laboratory Investigation

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“…1). [1][2][3][4] The major characteristics of ruptured plaques include a large lipid pool, a thin fibrous cap, and a low number of smooth muscle cells. 5 Furthermore, inflammation consisting of macrophages and lymphocytes is frequently present at the sites of plaque rupture, typically at plaque edges where the fibrous cap inserts into the arterial wall.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol crystals cause mechanical damage to biological membranes: A proposed mechanism of plaque rupture and erosion leading to arterial thrombosis

Abela

Aziz

2005

Clin Cardiol

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SummaryBackground: Plaque rupture and/or erosion is the leading cause of cardiovascular events; however, the process is not well understood. Although certain morphologic characteristics have been associated with ruptured plaques, these observations are of static histological images and not of the dynamics of plaque rupture. To elucidate the process of plaque rupture, we investigated the transformation of cholesterol from liquid to solid crystal to determine whether growing crystals are capable of injuring the plaque cap.Hypothesis: We hypothesized that during cholesterol crystallization the spatial configuration rapidly changes, causing forceful expansion of sharp-edged crystals that can damage the plaque cap.Methods: Two experiments were performed in vitro: first, cholesterol powder was melted in graduated cylinders and allowed to crystallize at room temperature. Volume changes from liquid to solid state were measured and timed. Second, thin biological membranes (20-40 µm) were put in the path of growing crystals to determine damage during crystallization.Results: As cholesterol crystallized, the peak volume increased rapidly by up to 45% over 3 min and sharp-tipped

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“…5 Human leukocyte antigen-DR expression, a marker of macrophage activation, is found more often on macrophages of ruptured plaques. 6,7 Moreover, fibrous caps that have ruptured not only have twice as many macrophages as unruptured fibrous caps but contain half as many smooth muscle cells, indicating that the ratio of vascular smooth muscle cells (VSMCs) to monocytes/macrophages (MMs) is altered markedly in ruptured plaques. The proportion of VSMCs undergoing apoptosis is increased significantly in unstable angina plaques versus stable angina.…”

mentioning

confidence: 99%

Activated Monocytes Induce Smooth Muscle Cell Death

et al. 2002

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Background — Plaque disruption is the inciting event for coronary thrombosis and acute coronary syndromes. Multiple factors influence plaque rupture, including the loss of vascular smooth muscle cells (VSMCs). We hypothesized that monocytes/macrophages (MMs) activated by macrophage colony-stimulating factor (M-CSF) are responsible for VSMC death. Methods and Results — VSMC apoptosis was markedly increased in the presence of both M-CSF and MMs (58.8±3.3%) compared with VSMCs plus M-CSF without MMs (15.7±1.5%, P ≤0.00005), VSMCs plus MMs without M-CSF (22.7±3.7%, P ≤0.0001), or control VSMCs alone (13.2±2.1%, P ≤0.0001). MM cell contact was required for M-CSF–stimulated killing of VSMCs, and MMs displayed an M-CSF concentration-dependent killing effect. Abciximab binds Mac-1 (CD11b/CD18) on MMs. When added to VSMCs exposed to MMs and M-CSF, abciximab (7 μg/mL) significantly reduced VSMC apoptosis (19.1±2.2%, P ≤0.0003). Therapeutic doses of tirofiban (0.35 μg/mL) and eptifibatide (5 μg/mL), which inhibit platelet glycoprotein (GP) IIb/IIIa but not Mac-1, did not block activated MM-induced VSMC apoptosis (65.0±3.4% and 51.3±2.5%, respectively). A recombinant anti–CD-18 antibody had an effect similar to that of abciximab (16.5±0.4%). Conclusions — These data suggest that monocytes and physiological concentrations of M-CSF trigger VSMC apoptosis. Abciximab and specific inhibitors of the Mac-1 receptor can antagonize this process.

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Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction

Cited by 418 publications

References 15 publications

Localization of Tissue Transglutaminase in Human Carotid and Coronary Artery Atherosclerosis: Implications for Plaque Stability and Progression

Localization of Tissue Transglutaminase in Human Carotid and Coronary Artery Atherosclerosis: Implications for Plaque Stability and Progression

Cholesterol crystals cause mechanical damage to biological membranes: A proposed mechanism of plaque rupture and erosion leading to arterial thrombosis

Activated Monocytes Induce Smooth Muscle Cell Death

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