Aerobic Exercise Prevents Pressure Overload-induced Heart Failure Associated With AMPK

Objective The purpose of this study was to investigate the effect of aerobic endurance excise on heart failure mice resulted from transverse aortic constriction(TAC)and to determine its mechanism.Methods 50 female C57BL/6 mice(8 weeks age)were randomly divided into sham control group(SC,n=10)?Sham exercise group(SE,n=10)?TAC control group(TC,n=15)and TAC exercise group(TE,n=15).The mice of SE group and TE group adapted to the treadmill training for one week and underwent aerobic endurance excise for 4 weeks at speed of 12m/min and lasting 60 min per time(6 times/week).After 5 weeks of intervention,theLVEDD?LVESD?EF and FS of left ventricle were detected by Cardiac ultrasound system.WGA staining technique was used to observe the cross-sectional area of ??cardiomyocytes.Sirius red staining technique was used to observe the degree of myocardial fibrosis.Protein expression of myocardial tissue was detected by Western blot.Results(1)Compared with the SC group,the LVEDD and LVESD in TC significantly increased(p<0.01),EF and FS in TC decreased significantly(p<0.01).Compared with the SE group,the LVEDD and LVESD in TE significantly increased(p<0.01),EF and FS in TE decreased significantly(p<0.01).Compared with the TC group,the LVEDD and LVESD in TE significantly decreased(p<0.01),EF and FS in TE increased significantly(p<0.01).(2)Compared with SC group,the LV mass,LV/BW and LV/TL in TC group were significantly increased(p<0.01);compared with SE group,the LV mass,LV/BW and LV/TL in TE group were significantly increased(p<0.01);compared with TC group,the LV mass,LV/BW and LV/TL in TE group were decreased(p<0.01).(3)Compared with SC group,the cross-sectional area of cardiomyocytes in TC group was significantly increased(p<0.01);Compared with SE group,the cross-sectional area of cardiomyocytes in TE group was significantly increased(p<0.01);Compared with TC group,the cross-sectional area of cardiomyocytes in the TE group decreased,but there was no significant difference.(4)There was significant myocardial fibrosis in TC group and TE group,and the degree of myocardial fibrosis was lower in TE group than in TC group.There was no obvious fibrosis in SC group and SE group.(5)Compared with SC group,the protein levels of ERR? in TC group were significantly decreased(p<0.01).Compared with SE group,the protein levels of ERR? decreased significantly(p<0.01).Compared with TC group,the protein levels of ERR? in TE group increased significantly(p<0.01).(6)Compared with SC group,the protein levels of AMPK,ACC phosphorylation and AMPK?1,AMPK?2,SIRT1,PGC1-? and ANP were significantly increased in TC group(p<0.01).Compared with SE group,the protein levels of AMPK,ACC phosphorylation and AMPK?1,AMPK?2,SIRT1,PGC1-? and ANP were significantly increased in TE group(p<0.01).Compared with TC group,the protein levels of AMPK,ACC phosphorylation and AMPK?1,AMPK?2,SIRT1,PGC1-?and ANP were significantly increased in TE group(p<0.01).Conclusions(1)TAC induces heart failure,resulting in decreased cardiac function,cardiomyocytes hypertrophy,and myocardial fibrosis.(2)Aerobic exercise increased the ejection fraction of heart failure mice induced by pressure overload,inhibited cardiomyocyte hypertrophy and myocardial fibrosis,and activated AMPK to prevent heart failure.(3)Pressure overload-induced heart failure is closely related to the AMPK/ACC signaling pathway.Exercise activates the AMPK signal pathway and plays a role in the prevention of heart failure.