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• W2025562215 abstract "Matrix metalloproteinase-14 (MMP-14) promotes vulnerable plaque morphology in mice, whereas tissue inhibitor of metalloproteinases-3 (TIMP-3) overexpression is protective.<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M1><mml:mrow><mml:msup><mml:mrow><mml:mtext>MMP-14</mml:mtext></mml:mrow><mml:mrow><mml:mtext>hi</mml:mtext></mml:mrow></mml:msup></mml:mrow></mml:math> <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M2><mml:mrow><mml:msup><mml:mrow><mml:mtext>TIMP-3</mml:mtext></mml:mrow><mml:mrow><mml:mtext>lo</mml:mtext></mml:mrow></mml:msup></mml:mrow></mml:math>rabbit foam cells are more invasive and more prone to apoptosis than<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M3><mml:mrow><mml:msup><mml:mrow><mml:mtext>MMP-14</mml:mtext></mml:mrow><mml:mrow><mml:mtext>lo</mml:mtext></mml:mrow></mml:msup></mml:mrow></mml:math> <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M4><mml:mrow><mml:msup><mml:mrow><mml:mtext>TIMP-3</mml:mtext></mml:mrow><mml:mrow><mml:mtext>hi</mml:mtext></mml:mrow></mml:msup></mml:mrow></mml:math>cells. We investigated the implications of these findings for human atherosclerosis. In vitro generated macrophages and foam-cell macrophages, together with atherosclerotic plaques characterised as unstable or stable, were examined for expression of MMP-14, TIMP-3, and inflammatory markers. Proinflammatory stimuli increased MMP-14 and decreased TIMP-3 mRNA and protein expression in human macrophages. However, conversion to foam-cells with oxidized LDL increased MMP-14 and decreased TIMP-3 protein, independently of inflammatory mediators and partly through posttranscriptional mechanisms. Within atherosclerotic plaques, MMP-14 was prominent in foam-cells with either pro- or anti-inflammatory macrophage markers, whereas TIMP-3 was present in less foamy macrophages and colocalised with CD206. MMP-14 positive macrophages were more abundant whereas TIMP-3 positive macrophages were less abundant in plaques histologically designated as rupture prone. We conclude that foam-cells characterised by high MMP-14 and low TIMP-3 expression are prevalent in rupture-prone atherosclerotic plaques, independent of pro- or anti-inflammatory activation. Therefore reducing MMP-14 activity and increasing that of TIMP-3 could be valid therapeutic approaches to reduce plaque rupture and myocardial infarction." @default.
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• W2025562215 date "2014-01-01" @default.
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• W2025562215 title "Relationship of MMP-14 and TIMP-3 Expression with Macrophage Activation and Human Atherosclerotic Plaque Vulnerability" @default.
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• W2025562215 doi "https://doi.org/10.1155/2014/276457" @default.
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