Dataset Information

CD36 Is a Matrix Metalloproteinase-9 Substrate That Stimulates Neutrophil Apoptosis and Removal During Cardiac Remodeling.

ABSTRACT: After myocardial infarction, the left ventricle undergoes a wound healing response that includes the robust infiltration of neutrophils and macrophages to facilitate removal of dead myocytes as well as turnover of the extracellular matrix. Matrix metalloproteinase (MMP)-9 is a key enzyme that regulates post-myocardial infarction left ventricular remodeling.Infarct regions from wild-type and MMP-9 null mice (n=8 per group) analyzed by glycoproteomics showed that of 541 N-glycosylated proteins quantified, 45 proteins were at least 2-fold upregulated or downregulated with MMP-9 deletion (all P<0.05). Cartilage intermediate layer protein and platelet glycoprotein 4 (CD36) were identified as having the highest fold increase in MMP-9 null mice. By immunoblotting, CD36 but not cartilage intermediate layer protein decreased steadily during the time course post-myocardial infarction, which identified CD36 as a candidate MMP-9 substrate. MMP-9 was confirmed in vitro and in vivo to proteolytically degrade CD36. In vitro stimulation of day 7 post-myocardial infarction macrophages with MMP-9 or a CD36-blocking peptide reduced phagocytic capacity. Dual immunofluorescence revealed concomitant accumulation of apoptotic neutrophils in the MMP-9 null group compared with wild-type group. In vitro stimulation of isolated neutrophils with MMP-9 decreased neutrophil apoptosis, indicated by reduced caspase-9 expression.Our data reveal a new cell-signaling role for MMP-9 through CD36 degradation to regulate macrophage phagocytosis and neutrophil apoptosis.

SUBMITTER: DeLeon-Pennell KY

PROVIDER: S-EPMC4758866 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CD36 Is a Matrix Metalloproteinase-9 Substrate That Stimulates Neutrophil Apoptosis and Removal During Cardiac Remodeling.

DeLeon-Pennell Kristine Y KY Tian Yuan Y Zhang Bai B Cates Courtney A CA Iyer Rugmani Padmanabhan RP Cannon Presley P Shah Punit P Aiyetan Paul P Halade Ganesh V GV Ma Yonggang Y Flynn Elizabeth E Zhang Zhen Z Jin Yu-Fang YF Zhang Hui H Lindsey Merry L ML

Circulation. Cardiovascular genetics 20151117 1

<h4>Background</h4>After myocardial infarction, the left ventricle undergoes a wound healing response that includes the robust infiltration of neutrophils and macrophages to facilitate removal of dead myocytes as well as turnover of the extracellular matrix. Matrix metalloproteinase (MMP)-9 is a key enzyme that regulates post-myocardial infarction left ventricular remodeling.<h4>Methods and results</h4>Infarct regions from wild-type and MMP-9 null mice (n=8 per group) analyzed by glycoproteomics ...[more]

PMID: 26578544

Similar Datasets

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.

Dataset Information

CD36 Is a Matrix Metalloproteinase-9 Substrate That Stimulates Neutrophil Apoptosis and Removal During Cardiac Remodeling.

Publications

CD36 Is a Matrix Metalloproteinase-9 Substrate That Stimulates Neutrophil Apoptosis and Removal During Cardiac Remodeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets