TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion.
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Cites background from "TLR2 and neutrophils potentiate end..."
...The latter critical transition seems to be a consequence of endothelial cell apoptosis, with localized endothelial denudation and the triggering of thrombus formation.(20) These superficial erosions typically occur on the surface of lesions containing abundant smooth muscle cells and proteoglycans, but few macrophages, and characteristically are associated with regions of disturbed blood flow....
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638 citations
Cites background from "TLR2 and neutrophils potentiate end..."
...Inflammatory activation of endothelial cells can disrupt VE-cadherin largely responsible for the integrity of the endothelial barrier function.(62) Activated endothelial cells can also express matrix metalloproteinases that can degrade the basement membrane and further interrupt endothelial barrier function....
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...Point-of-care assessment of such biomarkers would help render their use clinically practical in the triage of patients who present with ACS, with the goal of sparing some the need for urgent invasive diagnostic or therapeutic measures.(18,67,98) We then need rigorous clinical evaluation of targeted therapies guided by a more precise pathophysiological classification of ACS that reaches beyond our current dichotomous approach based on the ECG....
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References
3,869 citations
"TLR2 and neutrophils potentiate end..." refers background in this paper
...a discontinuous endothelial layer, contains abundant smooth muscle cells and proteoglycans/glycosaminoglycans—in particular hyaluronic acid and versican—and few macrophages.(2) Disruption of the endothelial layer likely contributes to such acute thrombotic complications....
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3,493 citations
"TLR2 and neutrophils potentiate end..." refers methods in this paper
...those with few SMCs but many inflammatory cells, and thin fibrous caps).(16) In this regard, we scrutinized our human endarterectomy tissue collection (n 1⁄4 295) and classified plaques by morphologic criteria as either rich in smooth muscle cells, or as ‘rupture-prone’ as described in the Methods section (see Supplementary material online, Figure S1)....
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1,329 citations
"TLR2 and neutrophils potentiate end..." refers background in this paper
...Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2....
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...In lesions prone to undergo erosion, lipoproteins and proteoglycans could serve as endogenous activators for TLR2.(9,10)...
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...The first consists of a phase of initial endothelial injury, mediated by TLR2....
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...In experimental atherosclerosis in mice, endothelial cells exhibit TLR2 in areas of disturbed blood flow, hyperlipidaemia increases TLR2 expression, and inhibition of this receptor reduces EC dysfunction produced by low shear stress.7 In humans, TLR2 protein increases substantially in the endothelium overlying atherosclerotic lesions.8 In lesions prone to undergo erosion, lipoproteins and proteoglycans could serve as endogenous activators for TLR2....
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...Gelatin zymographic analysis of supernatants of ECs showed significantly higher MMP2 activity in EC treated with disease-relevant endogenous ligands for TLR2 abundant in plaques that develop superficial erosions (Figure 5A).(9,10) Hyaluronan induced activity of MMP2 and MMP9 to levels similar to those seen with LTA....
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1,298 citations
1,214 citations
"TLR2 and neutrophils potentiate end..." refers background in this paper
...core and few macrophages in stark contrast to ruptured plaques.(1) Although impaired endothelial integrity characterizes eroded lesions, the underlying mechanisms remain obscure....
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...Human atheromata that undergo superficial erosion typically have many smooth muscle cells, but notably fewer macrophages than ruptured plaques.(1) We probed the mechanisms that might participate in endothelial loss in a collection of human lesions with morphologic characteristics ascribed to superficially eroded vs....
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...Many fatal myocardial infarctions result from superficial erosion of the intimawithout evidence offibrous cap rupture.(1) Erosions associate with female sex, younger age, smoking, hyper-triglyceridemia, and diabetes....
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