Exercise training ameliorates myocardial phenotypes in heart failure with preserved ejection fraction by changing N6-methyladenosine modification in mice model
机构：[1]Department of Biochemistry and Immunology, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China首都儿科研究所[2]Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, China首都儿科研究所[3]Beijing Municipal Key Laboratory of Child Development and Nutriomics, Beijing, China[4]Graduate School of Peking Union Medical College, Beijing, China[5]Beijing TongRen Hospital, Capital Medical University, Beijing, China首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Heart failure with preserved ejection fraction (HFpEF) shows complicated and not clearly defined etiology and pathogenesis. Although no pharmacotherapeutics have improved the survival rate in HFpEF, exercise training has become an efficient intervention to improve functional outcomes. Here, we investigated N6-methyladenosine (m(6)A) RNA methylation modification in a "two-hit " mouse model with HFpEF and HFpEF with exercise (HFpEF + EXT). The manner of m(6)A in HFpEF and HFpEF + EXT hearts was explored via m(6)A-specific methylated RNA immunoprecipitation followed by high-throughput and RNA sequencing methods. A total amount of 3992 novel m(6)A peaks were spotted in HFpEF + EXT, and 426 differently methylated sites, including 371 hypermethylated and 55 hypomethylated m(6)A sites, were singled out for further analysis (fold change > 2, p < 0.05). According to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, unique m(6)A-modified transcripts in HFpEF + EXT were associated with apoptosis-related pathway and myocardial energy metabolism. HFpEF + EXT had higher total m(6)A levels and downregulated fat mass and obesity-related (FTO) protein levels. Overexpression of FTO cancels out the benefits of exercise in HFpEF + EXT mice by promoting myocyte apoptosis, myocardial fibrosis and myocyte hypertrophy. Totally, m(6)A is a significant alternation of epitranscriptomic processes, which is also a potentially meaningful therapeutic target.
基金：
CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-008]; Public service development and reform pilot project of Beijing Medical Research Institute [BMR2019-11]; Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority [XTZD20180402]; National Key Research and Development Program of China [2018YFC1002503]
第一作者机构：[1]Department of Biochemistry and Immunology, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China[2]Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, China[3]Beijing Municipal Key Laboratory of Child Development and Nutriomics, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Biochemistry and Immunology, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China[2]Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Beijing, China[3]Beijing Municipal Key Laboratory of Child Development and Nutriomics, Beijing, China[4]Graduate School of Peking Union Medical College, Beijing, China[5]Beijing TongRen Hospital, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Liu Kai,Ju Wenhao,Ouyang Shengrong,et al.Exercise training ameliorates myocardial phenotypes in heart failure with preserved ejection fraction by changing N6-methyladenosine modification in mice model[J].FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY.2022,10:doi:10.3389/fcell.2022.954769.
APA：
Liu, Kai,Ju, Wenhao,Ouyang, Shengrong,Liu, Zhuo,He, Feng...&Wu, Jianxin.(2022).Exercise training ameliorates myocardial phenotypes in heart failure with preserved ejection fraction by changing N6-methyladenosine modification in mice model.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,10,
MLA：
Liu, Kai,et al."Exercise training ameliorates myocardial phenotypes in heart failure with preserved ejection fraction by changing N6-methyladenosine modification in mice model".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 10.(2022)
