Secreted frizzled-related protein 2 prevents pressure-overload-induced cardiac hypertrophy by targeting the Wnt/β-catenin pathway.

Content Provider	Europe PMC
Author	Wei, Wen-Ying Zhao, Qing Zhang, Wen-zhong Wang, Mao-jing Li, Yan Wang, Shi-zhong Zhang, Ning
Abstract	Background and aimSecreted frizzled-related protein 2 (sFRP2) has been reported to be involved in cardiovascular diseases. However, its role in cardiac hypertrophy induced by pressure overload is still elusive. We aimed to examine the role of sFRP2 in the development of cardiac hypertrophy in vivo and in vitro.Methods and resultsFollowing cardiac hypertrophy stimulated by aortic banding (AB), the expression of sFRP2 was downregulated in the hypertrophic ventricle. Adeno-associated virus 9 (AAV9) was injected through the tail vein to overexpress sFRP2 in the mouse myocardium. Overexpression of sFRP2 alleviated cardiomyocyte hypertrophy and interstitial fibrosis, as identified by the reduced cardiomyocyte cross-sectional area, heart weight/body weight ratio, and left ventricular (LV) collagen ratio. Additionally, sFRP2 decreased cardiomyocyte apoptosis induced by pressure overload. Western blot showed that sFRP2 prevented the expression of active β-catenin. The Wnt/β-catenin agonist LiCl (1 mmol/kg) abolished the inhibitory effects of sFRP2 on cardiac hypertrophy and apoptosis, as evidenced by the increased cross-sectional area and LV collagen ratio and the deterioration of echocardiographic data.ConclusionOur study indicated that decreased sFRP2 levels were observed in failing mouse hearts. Overexpression of sFRP2 attenuated myocyte hypertrophy and interstitial fibrosis induced by hypertrophic stimuli by inhibiting the Wnt/β-catenin pathway. We revealed that sFRP2 may be a promising therapeutic target for the development of cardiac remodeling.Electronic supplementary materialThe online version of this article (10.1007/s11010-020-03802-x) contains supplementary material, which is available to authorized users.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7338134&blobtype=pdf
ISSN	03008177
Journal	Molecular and Cellular Biochemistry [Mol Cell Biochem]
Volume Number	472
DOI	10.1007/s11010-020-03802-x
PubMed Central reference number	PMC7338134
Issue Number	1-2
PubMed reference number	32632611
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2020-07-06
Publisher Place	New York
Access Restriction	Open
Rights License	This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. © Springer Science+Business Media, LLC, part of Springer Nature 2020
Subject Keyword	Secreted frizzled-related protein 2 (sFRP2) Cardiac hypertrophy Fibrosis Apoptosis Pressure overload
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology