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.
Highlights
Ischemic heart disease (IHD) has been a leading cause to high morbidity and mortality in developed countries with increasing incidence in developing countries (Chan et al, 2011)
Our present study demonstrated for the first time that treatment with AFC1 compound effectively attenuates MI/Rinduced cardiac remodeling, accompanied by decreased platelet derived growth factor receptors (PDGFR) expression, oxidative stress, and inflammatory response in hearts post myocardial ischemia reperfusion (MI/R)
To determine the safety of AFC1 in vivo, we evaluated the pathology of liver, kidney, spleen, and lung from mice administrated with AFC1 compound for 14 days
Summary
Ischemic heart disease (IHD) has been a leading cause to high morbidity and mortality in developed countries with increasing incidence in developing countries (Chan et al, 2011). Effective prevention and treatment strategies to attenuate or reverse MI/R-induced remodeling is of great clinical value in IHD patients. It is reported that TSA can attenuate myocardial injury and improve ventricular remodeling post MI/R via reducing reactive oxygen species (ROS) generation in mitochondria (Zhou et al, 2003; Jin and Li, 2013; Jin et al, 2013). Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. 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
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