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Matrix metalloproteinase activation predicts amelioration of remodeling after dietary modification in injured arteries.

ABSTRACT: To establish and validate early noninvasive imaging of matrix metalloproteinase (MMP) activation for monitoring the progression of vascular remodeling and response to dietary modification.Apolipoprotein E(-/-) mice that were fed a high-fat diet underwent left common carotid artery wire injury. One week after surgery, a group of animals were withdrawn from the high-fat diet. The other group of animals continued that diet throughout the study. Micro single-photon emission computed tomographic (microSPECT)/CT imaging with RP805 (a (99m)Tc-labeled tracer targeting activated MMPs) was repeatedly performed at 2 and 4 weeks after surgery. Histological analysis at 4 weeks showed significant left carotid neointima formation, monocyte/macrophage infiltration, and upregulation of several MMPs, which were ameliorated by withdrawal from the high-fat diet. In vivo microSPECT/CT images visualized significant RP805 uptake, reflecting MMP activation, in the injured carotid arteries. MMP activation was reduced as early as 1 week after withdrawal from the high-fat diet and significantly correlated with neointimal area at 4 weeks after surgery.MMP activation predicts the progression of vascular remodeling and can track the effect of dietary modification after vascular injury.

SUBMITTER: Tavakoli S

PROVIDER: S-EPMC3005135 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Matrix metalloproteinase activation predicts amelioration of remodeling after dietary modification in injured arteries.

Tavakoli Sina S Razavian Mahmoud M Zhang Jiasheng J Nie Lei L Marfatia Ravi R Dobrucki Lawrence W LW Sinusas Albert J AJ Robinson Simon S Edwards D Scott DS Sadeghi Mehran M MM

Arteriosclerosis, thrombosis, and vascular biology 20101014 1

<h4>Objective</h4>To establish and validate early noninvasive imaging of matrix metalloproteinase (MMP) activation for monitoring the progression of vascular remodeling and response to dietary modification.<h4>Methods and results</h4>Apolipoprotein E(-/-) mice that were fed a high-fat diet underwent left common carotid artery wire injury. One week after surgery, a group of animals were withdrawn from the high-fat diet. The other group of animals continued that diet throughout the study. Micro si ...[more]

PMID: 20947820

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Project description:BackgroundVein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP2 contributes to vein wall remodeling after VT is unknown.MethodsStasis VT was produced by ligation of the inferior vena cava and tissue was harvested at 2, 8, and 21 days in MMP2 -/- and genetic wild type (WT) mice. Tissue analysis by immunohistochemistry, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and zymography was performed.ResultsThrombus resolution was less at 8 days in MMP2 -/- compared with WT, evidenced by a 51% increase in VT size (P < .01), and threefold fewer von Willebrand's factor positive channels (P < .05). In MMP2 -/- mice, the main phenotypic fibrotic differences occurred at 8 days post-VT, with significantly less vein wall collagen content (P = .013), fourfold lower procollagen III gene expression (P < .01), but no difference in procollagen I compared with WT. Decreased inflammation in MMP2 -/- vein walls was suggested by ∼ threefold reduced TNFα and IL-1β at 2 days and 8 days post-VT (P < .05). A fourfold increase in vein wall monocytes (P = .03) with threefold decreased apoptosis (P < .05), but no difference in cellular proliferation at 8 days was found in MMP2 -/- compared with WT. As increased compensatory MMP9 activity was observed in the MMP2 -/-mice, MMP2/9 double null mice had thrombus induced with VT harvest at 8 days. Consistently, twofold larger VT, a threefold decrease in vein wall collagen, and a threefold increase in monocytes were found (all P < .05). Similar findings were observed in MMP9 -/- mice administered an exogenous MMP2 inhibitor.ConclusionsIn stasis VT, deletion of MMP2 was associated with less midterm vein wall fibrosis and inflammation, despite an increase in monocytes. Consideration that VT resolution was impaired with MMP2 (and MMP2/9) deletion suggests direct inhibition will likely also require anticoagulant therapy.

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Matrix metalloproteinase activation predicts amelioration of remodeling after dietary modification in injured arteries.

Publications

Matrix metalloproteinase activation predicts amelioration of remodeling after dietary modification in injured arteries.

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