The compendium of matrix metalloproteinase expression in the left ventricle of mice following myocardial infarction

Abstract

Matrix metalloproteinases (MMPs) are proteolytic enzymes that break down extracellular matrix (ECM) components and have shown to be highly active in the myocardial infarction (MI) landscape. In addition to breaking down ECM products, MMPs modulate cytokine signaling and mediate leukocyte cell physiology. MMP-2, -7, -8, -9, -12, -14, and -28 are well studied as effectors of cardiac remodeling after MI. Whereas 13 MMPs have been evaluated in the MI setting, 13 MMPs have not been investigated during cardiac remodeling. Here, we measure the remaining MMPs across the MI time continuum to provide the full catalog of MMP expression in the left ventricle after MI in mice. We found that MMP-10, -11, -16, -24, -25, and -27 increase after MI, whereas MMP-15, -17, -19, -21, -23b, and -26 did not change with MI. For the MMPs increased with MI, the macrophage was the predominant cell source. This work provides targets for investigation to understand the full complement of specific MMP roles in cardiac remodeling. NEW & NOTEWORTHY To date, a number of matrix metalloproteinases (MMPs) have not been evaluated in the left ventricle after myocardial infarction (MI). This article supplies the missing knowledge to provide a complete MI MMP compendium.

Meta-Analysis of Extracellular Matrix Dynamics after Myocardial Infarction Using RNA-Sequencing Transcriptomic Database

“…Regarding the implication and dynamics of MMPs in ECM healing, MMP2, MMP3, MMP8, MMP9, MMP13, MMP14, and MMP28 have been widely described in the current literature, and results are in line with those obtained in this meta-analysis [ 21 , 23 , 24 , 25 , 26 , 27 ]. In contrast, the role of MMP10, MMP11, MMP15, MMP16, MMP17, MMP18, MMP23, MMP24, MMP25, and MMP27 post-MI has more recently been investigated via immunoblotting and immunohistochemistry [ 21 ], showing slight discrepancies with our results. This disagreement is most likely due to variations in study design: Kaminski et al determined mRNA expression only on macrophages and fibroblasts [ 21 ], while our results are based on the transcriptome of the whole cardiac tissue.…”

“…MMPs activity is controlled by specific inhibitors, named TIMPs, which are also involved in angiogenesis, cell proliferation, and apoptosis [ 19 , 20 ]. Scrutinizing the existence of both MMPs per se and peptide fragments generated by MMP cleavage is crucial to advance the understanding of post-MI heart failure development and hasten the discovery of potential predictive biomarkers [ 21 , 22 ]. In the current study, we focused on evaluating the dynamic variations in mRNA expression of genes encoding MMPs in the infarcted myocardium after ischemic insult.…”

Infarct in the Heart: What’s MMP-9 Got to Do with It?

“…ECM constituents play major roles in all phases of MI cardiac repair. Matrix metalloproteinases (MMPs) are a family of 25 proteolytic enzymes that collectively degrade all ECM components [ 18 , 19 , 20 ]. MMPs are major regulators of the ECM, conveyed into the infarct primarily by neutrophils and macrophages that begin infiltrating within minutes of the ischemic insult.…”

Faster skin wound healing predicts survival after myocardial infarction

“…All surviving animals were euthanized at MI day 7 . The 7-day follow-up time was selected because the kinetic rate of left ventricle (LV) remodeling (wall thinning and dilation) predominantly occurs over the first 7 days following MI ( 27 ).…”