Myocardial infarction‐relevant MMP‐12 interactions identified by correlation analysis

Abstract

Myocardial infarction (MI) occurs as a result of prolonged coronary artery occlusion that blocks the blood supply to the left ventricle. Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and play important roles in MI remodeling. MMP‐12 inhibition after MI in mice increases inflammation and exacerbates LV dysfunction and wall thinning, indicating a potential protective role. Here, we used the Mouse Heart Attack Research Tool 1.0 (mHART 1.0) database to correlate MMP‐12 expression over the MI time course (days 0, 1, 3, 5, and 7 MI) with expression of 165 ECM and cytokine genes in the LV infarct. A total of 39 records in the database had complete information on gene array data, echocardiography, and necropsy. There were a total of 42 genes that correlated with MMP‐12 (all p<0.05). The most significant correlations were between MMP‐12 and MMP‐10 (r= 0.92; p= 1.38E‐16) or Ctnna2 (r=0.92; p= 1.50E‐16), followed by TIMP‐1 (r=0.90; p= 6.42E‐15). Through Enrichr analysis for transcription factor profiling, Yap 1 was the most enriched (combined score=10.27, p value=0.002), indicating strong Hippo signaling. Combined, our results reveal novel candidate interactors with MMP‐12 and indicate Hippo signaling through Yap1 may be a key regulated MMP‐12 feature in the MI left ventricle.Support or Funding InformationNIH HL075360, NIH GM104357, GM114833, GM115428, HL051971, HL129823, and VA 5I01BX000505This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.