Abstract P2107: Latent Transforming Growth Factor Binding Protein - 2 Deficiency Improves Cardiac Function Post-Myocardial Infarction

Abstract

Cardiac fibrosis and myocardial stiffening are key factors contributing to deteriorating cardiac function during heart failure, especially after myocardial infarction (MI). In the myocardium, cardiac fibroblasts (CFs) are the main cell type driving excess extracellular matrix (ECM) protein deposition, leading to pathological remodelling of the heart. Latent Transforming Growth Factor Binding Protein 2 (LTBP2) is one of the ECM proteins released as part of the fibrotic response and is significantly upregulated in all types of heart failure. Although LTBP2 belongs to a family of proteins that regulate the release of Transforming Growth Factor - β; (TGF-β;) in the ECM, it doesn’t interact with TGF-β;. Nonetheless, LTBP2 is shown to play a role in the progression of fibrosis following heart failure by contributing to CFs activation. Therefore, we hypothesized that in the absence of LTBP2, the heart would have improved cardiac function following MI. We used LTBP2 knockout (KO) C57BL/6 mice and modelled MI by ligating the left anterior descending artery. Echocardiography was performed to analyze the cardiac function in KO and wild-type (WT) infarcted hearts at 7 and 28 days post-MI. KO mice showed significantly better ejection fractions (KO = 24.1±4.9% vs. WT = 9.2±1.4%, p-value < 0.01) and fractional shortening 28 days post-MI compared to WT mice. In conclusion, our findings show that LTBP2 contributes to the deteriorating cardiac function following MI suggesting that targeting LTBP2 may have therapeutic potential. As LTBP2 is known to be a part of the fibrotic response, future studies will investigate the fibrotic profile of WT and KO infarcted hearts using histology and CFs-specific RNA sequencing to highlight the underlying differences leading to the observed cardiac function.