PMID- 32632611 OWN - NLM STAT- MEDLINE DCOM- 20210317 LR - 20240212 IS - 1573-4919 (Electronic) IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 472 IP - 1-2 DP - 2020 Sep TI - Secreted frizzled-related protein 2 prevents pressure-overload-induced cardiac hypertrophy by targeting the Wnt/beta-catenin pathway. PG - 241-251 LID - 10.1007/s11010-020-03802-x [doi] AB - BACKGROUND AND AIM: Secreted 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 RESULTS: Following 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 beta-catenin. The Wnt/beta-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. CONCLUSION: Our 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/beta-catenin pathway. We revealed that sFRP2 may be a promising therapeutic target for the development of cardiac remodeling. FAU - Wei, Wen-Ying AU - Wei WY AD - Department of Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, China. FAU - Zhao, Qing AU - Zhao Q AD - Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China. FAU - Zhang, Wen-Zhong AU - Zhang WZ AD - Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China. FAU - Wang, Mao-Jing AU - Wang MJ AD - Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China. FAU - Li, Yan AU - Li Y AD - Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China. FAU - Wang, Shi-Zhong AU - Wang SZ AD - Department of Cardiovascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China. FAU - Zhang, Ning AU - Zhang N AUID- ORCID: 0000-0003-1995-7251 AD - Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China. zhangningqdfy@yeah.net. LA - eng GR - 3094/the Youth Fund of the Affiliated Hospital of Qingdao University/ PT - Journal Article DEP - 20200706 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Membrane Proteins) RN - 0 (Sfrp2 protein, mouse) RN - 0 (Sfrp2 protein, rat) RN - 0 (Wnt Proteins) RN - 0 (beta Catenin) SB - IM MH - Animals MH - Animals, Newborn MH - Cardiomegaly/etiology/metabolism/pathology/*prevention & control MH - Disease Models, Animal MH - Male MH - Membrane Proteins/genetics/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Pressure MH - Rats MH - Rats, Sprague-Dawley MH - Wnt Proteins/genetics/*metabolism MH - beta Catenin/genetics/*metabolism PMC - PMC7338134 OTO - NOTNLM OT - Apoptosis OT - Cardiac hypertrophy OT - Fibrosis OT - Pressure overload OT - Secreted frizzled-related protein 2 (sFRP2) COIS- The authors declare that they have no conflicts of interest. EDAT- 2020/07/08 06:00 MHDA- 2021/03/18 06:00 PMCR- 2020/07/06 CRDT- 2020/07/08 06:00 PHST- 2019/11/15 00:00 [received] PHST- 2020/06/18 00:00 [accepted] PHST- 2020/07/08 06:00 [pubmed] PHST- 2021/03/18 06:00 [medline] PHST- 2020/07/08 06:00 [entrez] PHST- 2020/07/06 00:00 [pmc-release] AID - 10.1007/s11010-020-03802-x [pii] AID - 3802 [pii] AID - 10.1007/s11010-020-03802-x [doi] PST - ppublish SO - Mol Cell Biochem. 2020 Sep;472(1-2):241-251. doi: 10.1007/s11010-020-03802-x. Epub 2020 Jul 6.