AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway

Abstract

Background: Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of AFC1 compound that is similar to TSA structure in murine MI/R models. We found that AFC1 had a comparable effect of improving murine cardiac function after MI/R while it was superior to TSA in safety profile. Administration of AFC1 reduced reactive oxygen species (ROS) production, inflammatory cells infiltration, and the expression of platelet derived growth factor receptors (PDGFR) in infarcted myocardium. Treatment with AFC1 also attenuated MI/R-induced cardiac remodeling and contributed to the recovery of cardiac function. Additionally, AFC1 reversed the elevation of PDGFR expression induced by PDGF-AB in both neonatal rat cardiomyocytes (NCMs) and neonatal rat cardiac fibroblasts (NCFs) and suppressed PDGF-AB induced NCM hypertrophy via STAT3 pathway and NCF collagen synthesis through p38-MAPK signaling in vitro. Similarly, AFC1 may contribute to the recovery of cardiac function in mice post MI/R via suppressing STAT signaling. Our results confirmed that AFC1 exerts anti-hypertrophic and anti-fibrotic effects against MI/R-induced cardiac remodeling, and suggest that AFC1 may have a promising potential in improving the outcome of patients who suffered from MI/R.

Profiling and Molecular Mechanism Analysis of Long Non-Coding RNAs and mRNAs in Pulmonary Arterial Hypertension Rat Models

“…The functional analysis demonstrated the potential roles of lncRNAs, which mainly enriched in inflammatory and immune response. Several key genes, including LGALS3 ( Schroeder et al, 2020 ), PDGFC ( Liu et al, 2019 ), NFIL3 ( Kashiwada et al, 2010 ) and so on, were further verified in this study. Activation of immune cells and release of proinflammatory factors in system and microenvironment could be powerful contributors to numerous cardiovascular diseases.…”