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Carnosic acid protects against pressure overloadinduced cardiac remodelling by inhibiting the AKT/GSK3β/NOX4 signalling pathway

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Oxidative stress and apoptosis serve an important role in the development of pressure overloadinduced cardiac remodelling. Carnosic acid (CA) has been found to exert antioxidant and antiapoptotic effects. The present study investigated the underlying mechanism of CA protection and whether this effect was exerted against pressure overloadinduced cardiac remodelling. Aortic banding (AB) surgery was performed to induce cardiac remodelling. Mice were randomly divided into four groups (n=15/group): i) Sham + vehicle; ii) sham + CA; iii) AB + vehicle; and iv) AB + CA. After 2 days of AB, 50 mg kg CA was administered orally for 12 days. Echocardiography, histological analysis and molecular biochemistry techniques were performed to evaluate the roles of CA. CA treatment decreased cardiac hypertrophy, fibrosis, oxidative stress and apoptosis in mice challenged with pressure overload. CA also decreased the crosssectional area of cardiomyocytes and the mRNA and protein expression levels of hypertrophic markers. Furthermore, CA treatment decreased collagen deposition, αsmooth muscle actin expression and the mRNA and protein expression of various fibrotic markers. Additionally, CA reversed the ABmediated increase in NAPDH oxidase (NOX) 2, NOX4 and 4hydroxynonenal levels. The number of apoptotic cells was decreased following CA treatment following under conditions of pressure overload. CA also suppressed the activation of AKT and glycogen synthase kinase 3 β (GSK3β) in mice challenged with AB. The present results suggested that CA could inhibit pressure overloadinduced cardiac hypertrophy and fibrosis by suppressing the AKT/GSK3β/NOX4 signalling pathway. Therefore, CA may be a promising therapy for cardiac remodelling.
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Document Type: Research Article

Affiliations: Department of Cardiology, Taihe Hospital of Shiyan, Affiliated to Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China

Publication date: October 1, 2020

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  • Experimental and Therapeutic Medicine aims to ensure the expedient publication, in both print and electronic format, of studies relating to biology, gene therapy, infectious disease, microbiology, molecular cardiology and molecular surgery. The journal welcomes studies pertaining to all aspects of molecular medicine, and studies relating to in vitro or in vivo experimental model systems relevant to the mechanisms of disease are also included.

    All materials submitted to this journal undergo the appropriate review via referees who are experts in this field. All materials submitted follow international guidelines with regard to approval of experiments on humans and animals.
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