PMID- 30153824 OWN - NLM STAT- MEDLINE DCOM- 20181116 LR - 20201209 IS - 1476-511X (Electronic) IS - 1476-511X (Linking) VI - 17 IP - 1 DP - 2018 Aug 28 TI - Sfrp1 attenuates TAC-induced cardiac dysfunction by inhibiting Wnt signaling pathway- mediated myocardial apoptosis in mice. PG - 202 LID - 10.1186/s12944-018-0832-3 [doi] LID - 202 AB - BACKGROUND: Hemodynamic overload causes cardiac hypertrophy leading to heart failure. Wnt signaling pathway was reported activated in heart failure. Secreted frizzled related protein 1 (Sfrp1) is a suppressor of Wnt signaling activation. The aim of the present study was to investigate the protective effect of Sfrp1 on hemodynamic overload- induced cardiac dysfunction. METHODS: A mice transverse aortic constriction (TAC)- induced heart failure model was established. A recombinant adeno-associated virus 9 (AAV9) vector was used to deliver Sfrp1 gene into myocardium. Fluorescence and immunohistochemistry staining was used to evaluate the effectiveness of viral vector delivery. Invasive hemodynamic examination was used to evaluate cardiac systolic and diastolic functions. Myocardium apoptosis was detected by TUNEL assay. The expression levels of Sfrp1, beta-catenin, caspase3, Bax, Bcl-2 and c-Myc were measured by Western blotting. RESULTS: Increased mean arterial pressure and impaired cardiac function confirmed the establishment of TAC model. Sfrp1 protein expression was effectively increased in myocardium of mice treated with AAV9-Sfrp1 viral vector. The viral vector administration improved both systolic and diastolic cardiac functions by reducing myocardial apoptosis in TAC mice. The expression levels of beta-catenin, caspase3 and Bax were significantly reduced while the expression levels of Bcl-2 and c-Myc were dramatically increased in myocardium by the viral vector treatment in TAC mice. CONCLUSIONS: AAV9 viral vector delivered sfrp1 expression gene into myocardium, which attenuated TAC-induced cardiac dysfunction by inhibiting Wnt signaling pathway activation- mediated apoptosis. FAU - Pan, Shuo AU - Pan S AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. AD - 1st Department of Cardiology, People's Hospital of Shaanxi Province, Xi'an, Shaanxi Province, China. FAU - Zhao, Xiujuan AU - Zhao X AD - Ultrasonic Center, Northwest Women and Children's Hospital, Xi'an, Shaanxi Province, China. FAU - Wang, Xu AU - Wang X AD - Student Brigade, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Tian, Xin AU - Tian X AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Wang, Yuanbo AU - Wang Y AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Fan, Rong AU - Fan R AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Feng, Na AU - Feng N AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Zhang, Shumiao AU - Zhang S AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Gu, Xiaoming AU - Gu X AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Jia, Min AU - Jia M AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Li, Juan AU - Li J AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Yang, Lu AU - Yang L AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Wang, Kaiyan AU - Wang K AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. FAU - Guo, Haitao AU - Guo H AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. haitaoguo@fmmu.edu.cn.com. FAU - Pei, Jianming AU - Pei J AD - Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi Province, China. jmpei8@fmmu.edu.cn. LA - eng GR - 2017M623371/China Postdoctoral Science Foundation/ GR - 81500308/National Natural Science Foundation of China/ GR - 81770243/National Natural Science Foundation of China/ GR - 81470248/National Natural Science Foundation of China/ GR - 81270102/National Natural Science Foundation of China/ GR - 2016KTCL03-11/grant from Shaanxi Province/ PT - Journal Article DEP - 20180828 PL - England TA - Lipids Health Dis JT - Lipids in health and disease JID - 101147696 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Proteins) RN - 0 (WD repeat containing planar cell polarity effector) RN - 0 (beta Catenin) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Aorta/*metabolism/*physiopathology MH - *Apoptosis MH - Constriction, Pathologic MH - Dependovirus/metabolism MH - Green Fluorescent Proteins/metabolism MH - Intracellular Signaling Peptides and Proteins MH - Mice, Inbred C57BL MH - Myocardium/*metabolism/*pathology MH - Proteins/*metabolism MH - *Wnt Signaling Pathway MH - beta Catenin/metabolism PMC - PMC6114876 OTO - NOTNLM OT - Apoptosis OT - Heart failure OT - Sfrp1 OT - Viral vector OT - Wnt signaling pathway COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study protocol was approved by the Ethics Committee of Fourth Military Medical University. CONSENT FOR PUBLICATION: All authors have approved the final manuscript for publication. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/08/30 06:00 MHDA- 2018/11/18 06:00 PMCR- 2018/08/28 CRDT- 2018/08/30 06:00 PHST- 2018/05/01 00:00 [received] PHST- 2018/07/19 00:00 [accepted] PHST- 2018/08/30 06:00 [entrez] PHST- 2018/08/30 06:00 [pubmed] PHST- 2018/11/18 06:00 [medline] PHST- 2018/08/28 00:00 [pmc-release] AID - 10.1186/s12944-018-0832-3 [pii] AID - 832 [pii] AID - 10.1186/s12944-018-0832-3 [doi] PST - epublish SO - Lipids Health Dis. 2018 Aug 28;17(1):202. doi: 10.1186/s12944-018-0832-3.