Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart  

作　　者：WANG YaBin MA Sai WANG Qiang HU WenXing WANG DongJuan LI XiuJuan SU Tao QIN Xing ZHANG XiaoTian MA Ke CHEN JiangWei XIONG LiZe CAO Feng 

机构地区：[1]Department of Cardiology, Xijing Hospital, Fourth Military Medical University [2]Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University [3]Department of Cardiology, PLA General Hospital

出　　处：《Science China(Life Sciences)》2014年第2期201-208,共8页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(81270168,81090274,81325009,81090270 and F Cao BWS12J037);Innovation Team Development Grant by Ministry of Education of China(2010CXTD01,IRT1053);the National Basic Research Program of China(2012CB518101)

摘　　要：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 CB2receptor activation in enhancing myocardial repair.Our results revealed that CB2receptor 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-αand 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.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 CB2receptor activation in enhancing myocardial repair.Our results revealed that CB2receptor 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-αand 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.

关 键 词：CB2 receptor cardiac progenitor cells endogenous cardiac regeneration 

分 类 号：R542.22[医药卫生—心血管疾病]