A Retinoic Acid Receptorβ₂Agonist Improves Cardiac Function in a Heart Failure Model

Abstract

We previously demonstrated that the selective retinoic acid β2-receptor (RARβ2) agonist AC261066 reduces oxidative stress in an ex-vivo murine model of ischemia/reperfusion. We hypothesized that by decreasing oxidative stress and consequent fibrogenesis, AC261066 could attenuate the development of contractile dysfunction in post-ischemic heart failure (HF). We tested this hypothesis in-vivo using an established murine model of myocardial infarction (MI), obtained by permanent occlusion of the left anterior descending coronary artery. Treating mice with AC261066 in drinking water significantly attenuated the post-MI deterioration of echocardiographic indices of cardiac function, diminished remodeling, and reduced oxidative stress, as evidenced by a decrease in malondialdehyde level and p38 mitogen-activated protein kinase expression in cardiomyocytes. The effects of AC261066 were also associated with a decrease in interstitial fibrosis, as shown by a marked reduction in collagen deposition and α-smooth muscle actin expression. In cardiac murine fibroblasts subjected to hypoxia, AC261066 reversed hypoxia-induced decreases in SOD2 and ANGPTL4 transcriptional levels as well as the increase in NOX-2 mRNA, demonstrating that the post-MI cardioprotective effects of AC261066 are associated with an action at the fibroblast level. Thus, AC261066 alleviates post-MI cardiac dysfunction by modulating a set of genes involved in the oxidant/antioxidant balance. These AC261066 responsive genes diminish interstitial fibrogenesis and remodeling. Since MI is a This article has not been copyedited and formatted. The final version may differ from this version.

L-Arginine Enhances the Effects of Cardiac Rehabilitation on Physical Performance: New Insights for Managing Cardiovascular Patients During the COVID-19 Pandemic

“…Our results do not allow any speculation on the mechanisms underlying the favorable effect of Larginine on CR induced improvement in physical capacity. However, AMI leads to endothelial dysfunction with inflammation and oxidative stress, contributing to physical impairment, hospitalizations, and mortality (Odegaard et al, 2016;Steven et al, 2019;Kibel et al, 2020;Mone et al, 2021;Tang et al, 2021;Thompson et al, 2021). In this scenario, adding L-Arginine in a post-AMI cohort is supported by a strong rationale, inasmuch as L-Arginine, among its pleiotropic effects, has been shown to counteract endothelial dysfunction, inflammation, and oxidative stress (Mabalirajan et al, 2010;van der Zwan et al, 2011;Hong et al, 2018;Qiu et al, 2019;Fiorentino et al, 2021).…”

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Nanocontainer derived from silkworm carotenoprotein for carotenoid extraction and presentation in biotechnology and biomedical applications

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