Key result
Deletion of the gene encoding MMCP-4 (Mcpt4) markedly reduced late infarct size by suppressing IGF-1 degradation, diminishing cardiac dysfunction and adverse structural remodeling in mice.
Why the study?
Does deletion of the MMCP-4 gene reduce infarct size and adverse cardiac remodeling in a mouse model of myocardial infarction?
Does deletion of the MMCP-4 gene reduce infarct size and adverse cardiac remodeling in a mouse model of myocardial infarction?
Deletion of MMCP-4 in mice reduces late infarct size and adverse remodeling after myocardial infarction by preventing IGF-1 degradation, suggesting chymase inhibition as a potential therapeutic target.
Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in postischemic heart disease.
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Tejada et al. (2016) studied Myocardial infarction. Deletion of the gene encoding MMCP-4 (Mcpt4) was evaluated on Late infarct size, cardiac dysfunction, and adverse structural remodeling. Deletion of the gene encoding MMCP-4 (Mcpt4) markedly reduced late infarct size by suppressing IGF-1 degradation, diminishing cardiac dysfunction and adverse structural remodeling in mice.
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