title: Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart.
abstract: Cannabinoid receptor type 2 (CB2) activation is recently reported to promote proliferation of some types of resident stem cells (e.g., hematopoietic stem/progenitor cell or neural progenitor cell). Resident cardiac progenitor cell (CPC) activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction (MI). This study aims to explore the role and possible mechanisms of CB2 receptor activation in enhancing myocardial repair. Our results revealed that CB2 receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation. AM1241 also decreased serum levels of MDA, TNF-α and IL-6 after MI. In addition, AM1241 can ameliorate left ventricular ejection fraction and fractional shortening, and reduce fibrosis. Moreover, AM1241 treatment markedly increased p-Akt and HO-1 expression, and promoted Nrf-2 nuclear translocation. However, PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241. In conclusion, AM1241 could induce myocardial regeneration and improve cardiac function, which might be associated with PI3K/Akt/Nrf2 signaling pathway activation. Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: YaBin
authors.initials: Y
authors.lastname: Wang
authors.forename: Sai
authors.initials: S
authors.lastname: Ma
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: WenXing
authors.initials: W
authors.lastname: Hu
authors.forename: DongJuan
authors.initials: D
authors.lastname: Wang
authors.forename: XiuJuan
authors.initials: X
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.forename: Xing
authors.initials: X
authors.lastname: Qin
authors.forename: XiaoTian
authors.initials: X
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Ma
authors.forename: JiangWei
authors.initials: J
authors.lastname: Chen
authors.forename: LiZe
authors.initials: L
authors.lastname: Xiong
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000503:physiopathology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000502:physiology*; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C439263:AM 1241; D002186:Cannabinoids; D050676:Core Binding Factor Alpha 2 Subunit; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D043885:Receptor, Cannabinoid, CB2; C493726:Runx1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt