Long-term oral atazanavir attenuates myocardial infarction-induced cardiac fibrosis.

Long-term oral atazanavir attenuates myocardial infarction-induced cardiac fibrosis. Eur J Pharmacol. 2018 Mar 29;: Authors: Zhang G, Zhang X, Li D, Tian J, Jiang W Abstract Atazanavir is an antiretroviral medication used to treat and prevent HIV/AIDS, but its effects on cardiac fibrosis are unknown. The aim of this study was to determine the effects of atazanavir on myocardial infarction (MI)-induced cardiac fibrosis in rats and used a TLR 9 antagonist, hydroxychloroquine (HCQ) to elucidate the potential mechanism in vitro. The results indicated that atazanavir significantly attenuated CoCl2-induced neonatal rat cardiac fibroblast (rCFs) proliferation in a concentration-dependent manner. Treatment of rCFs with atazanavir 1-10µM blocked CoCl2-induced nuclear factor kappaB phosphorylation (p-NF-κB), p-IκBα and high-mobility group box 1 (HMGB1) expression. Treatment of rCFs with atazanavir 3µM blocked HMGB1 downstream, p-NF-κB by blocking HMGB1 binds to toll-like receptor 9 (TLR 9). Intragastric administration of atazanavir sulfate 30mg/k ameliorated changes in the left ventricular systolic pressure (LVSP), +dp/dtmax, and -dp/dtmax after 4 weeks. This was associated with attenuation of α-SMA, HMGB1, p-NF-κB, TLR 9, collagen I, collagen III expression and hydroxyproline (Hyp) content in ischemic myocardial tissue. Additionally, continuous intragastric administration of atazanavir for 28 days attenuated cardiac remodeling. These ...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research