Lipid and cellular constituents of unstable human aortic plaques

Davies, Michael J.; Woolf, N. J.; Rowles, P M; Richardson, P. D.

doi:10.1007/978-3-642-85660-0_3

Cited by 31 publications

(24 citation statements)

References 18 publications

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“…Both midkine (Kojima et al, 1997) and vitronectin (Sane et al, 1990) are much more readily cross-linked by TG in the presence of sulfaterich glycosaminoglycans. Interestingly, the content of sulfated glycosaminoglycans is reduced in the cap of the unstable plaque (Davies et al, 1994).…”

Section: Tg In Atherosclerosismentioning

confidence: 99%

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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: Tg In Atherosclerosismentioning

confidence: 99%

“…SMC are the source of collagen, elastin, and glycosaminoglycans in the cap. Consequently, a reduction in the SMC content leads to weakening of the fibrous cap through loss of these matrix constituents (Davies et al, 1994).…”

mentioning

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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“…Inflammatory cell accumulation characterizes disrupted plaques. 23,24 Production of apoptosis-promoting mediators by activated inflammatory or immune cells may lead to the death of vascular SMCs, which may in turn weaken and destabilize the plaques. Indeed, in 1995, we dubbed SMCs "the guardians of the integrity of the plaque's fibrous cap," and we originally proposed a role for SMC dropout that was due to apoptosis in the thinning of the fibrous cap.…”

Section: Apoptosis and Stability Of Atherosclerotic Plaquesmentioning

confidence: 99%

Progression of Atheroma

Geng

Libby

2002

ATVB

250

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Abstract-Traditional thinking accorded a major role to deranged cell proliferation as a determinant of the abnormal cellularity of atheroma. However, studies conducted in several laboratories have documented the occurrence of disordered apoptosis during atherogenesis, leading to the death of lipid-rich foam cells (promoting lipid-core formation) and depletion of vascular smooth muscle cells (fostering fragility of the fibrous cap). A complex interplay of environmental factors and endogenous proteins regulates apoptosis and contributes to the struggle between cell death and procreation in atherosclerosis. In addition to a variety of growth factors, chemically modified lipids, reactive oxygen species, proinflammatory cytokines, and Fas ligand produced by activated immune cells may influence cell viability through a diversity of pathways, including the caspase cascade, the Bcl-2 protein family, and the oncogene/antioncogene system. A clarification of the molecular mechanisms responsible for vascular cell death may aid in the development of novel therapeutic strategies to treat atherosclerosis and its complications, including the acute coronary syndromes.

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“…Plaque rupture is often associated with the breakdown of ECM in the shoulder region of a plaque (4,5 ). This is supported by the observation that vulnerable plaques, relative to stable plaques, contain low amounts of ECM (6,7 ). ECM breakdown is mediated by proteinases, in particular MMPs, which are being overexpressed in the shoulder region of atherosclerotic plaques (3 ).…”

mentioning

confidence: 99%

Increased Plasma Concentration of Matrix Metalloproteinase-7 in Patients with Coronary Artery Disease

Nilsson

Jonasson

Nijm³

et al. 2006

Clinical Chemistry

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Background: Plaque rupture is often associated with breakdown of the extracellular matrix in the shoulder region of a plaque. We tested whether plasma concentrations of various matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) could serve as markers for plaque instability as well as relationships between plasma MMPs and inflammatory markers. Methods: The study group included 65 men with angiographically verified CAD (45 with stable and 20 with unstable CAD) and 28 healthy controls. Circulating MMP, TIMP-1, C-reactive protein, and cytokine concentrations were measured by ELISA. Leukocyte subtype counts in whole blood were determined, and T-cell subsets and natural killer cells were measured by flow cytometry. Differences in continuous variables between groups were tested by ANOVA with the Scheffé F-test used as a post hoc test, and correlations were analyzed by a linear regression method. Results: The plasma concentration of MMP-7 was increased in patients with stable and unstable CAD, whereas MMP-2 and -3 concentrations were decreased. The plasma concentration of TIMP-1 was significantly increased in patients with unstable CAD. MMP-2, -3, and -7 showed no correlations with established markers of inflammation. However, MMP-2 correlated positively

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Lipid and cellular constituents of unstable human aortic plaques

Cited by 31 publications

References 18 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

Progression of Atheroma

Increased Plasma Concentration of Matrix Metalloproteinase-7 in Patients with Coronary Artery Disease

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