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Matrix metalloproteinase-28 deletion exacerbates cardiac dysfunction and rupture after myocardial infarction in mice by inhibiting M2 macrophage activation.

ABSTRACT: Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix responses in cardiac aging, but the roles of MMP-28 after myocardial infarction (MI) have not been explored.To determine the impact of MMP-28 deletion on post-MI remodeling of the left ventricle (LV).Adult C57BL/6J wild-type (n=76) and MMP null (MMP-28((-/-)), n=86) mice of both sexes were subjected to permanent coronary artery ligation to create MI. MMP-28 expression decreased post-MI, and its cell source shifted from myocytes to macrophages. MMP-28 deletion increased day 7 mortality because of increased cardiac rupture post-MI. MMP-28(-/-) mice exhibited larger LV volumes, worse LV dysfunction, a worse LV remodeling index, and increased lung edema. Plasma MMP-9 levels were unchanged in the MMP-28((-/-)) mice but increased in wild-type mice at day 7 post-MI. The mRNA levels of inflammatory and extracellular matrix proteins were attenuated in the infarct regions of MMP-28(-/-) mice, indicating reduced inflammatory and extracellular matrix responses. M2 macrophage activation was impaired when MMP-28 was absent. MMP-28 deletion also led to decreased collagen deposition and fewer myofibroblasts. Collagen cross-linking was impaired as a result of decreased expression and activation of lysyl oxidase in the infarcts of MMP-28(-/-) mice. The LV tensile strength at day 3 post-MI, however, was similar between the 2 genotypes.MMP-28 deletion aggravated MI-induced LV dysfunction and rupture as a result of defective inflammatory response and scar formation by suppressing M2 macrophage activation.

SUBMITTER: Ma Y

PROVIDER: S-EPMC3597388 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Matrix metalloproteinase-28 deletion exacerbates cardiac dysfunction and rupture after myocardial infarction in mice by inhibiting M2 macrophage activation.

Ma Yonggang Y Halade Ganesh V GV Zhang Jianhua J Ramirez Trevi A TA Levin Daniel D Voorhees Andrew A Jin Yu-Fang YF Han Hai-Chao HC Manicone Anne M AM Lindsey Merry L ML

Circulation research 20121220 4

<h4>Rationale</h4>Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix responses in cardiac aging, but the roles of MMP-28 after myocardial infarction (MI) have not been explored.<h4>Objective</h4>To determine the impact of MMP-28 deletion on post-MI remodeling of the left ventricle (LV).<h4>Methods and results</h4>Adult C57BL/6J wild-type (n=76) and MMP null (MMP-28((-/-)), n=86) mice of both sexes were subjected to permanent coronary artery ligation to create M ...[more]

PMID: 23261783

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Matrix metalloproteinase-28 deletion exacerbates cardiac dysfunction and rupture after myocardial infarction in mice by inhibiting M2 macrophage activation.

Publications

Matrix metalloproteinase-28 deletion exacerbates cardiac dysfunction and rupture after myocardial infarction in mice by inhibiting M2 macrophage activation.

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