Effects Of Exercise Training On Mitochondria In Heart Failure: Molecular Physiology Adaptation Of Mitochondrial Biogenesis And Fusion/fission Dynamics

Aims:Mitochondrial dysfunction is a major factor in heart failure(HF).The aim of present study was to to investigate 1) the mitochondrial function, mitochondrial biogenesis and mitochondrial dynamics in the failing myocardium post myocardial infarction.2) the effects of aerobic exercise on the cardiac function and the mitochondrial function,biogenesis and dynamics in the cardiac muscle after myocardial infarction.Methods:Myocardial infarction(MI) was obtained by left descending coronary artery ligation.Sham operation was performed in another group without coranay ligation.4 weeks after the operation,the animals were divided into 4 groups:sham operatin control group(sham),sham operation plus exercise group(sham+E), myocardial infarction group(MI),myocardial infarction plus exercise group(MI+E). Exercise groups were trained on treadmill for 8 weeks,5 days a week.14m/min, 40min/day.LVIDs,LVIDd,ejection fraction(EF),cardial output(CO),heart rate (HR) were measured with M-mode echocardiograms.Mitochondrial oxygen consumption was measured in respiration of state 3(R3) and state 4(R4),the respiratory control ration(RCR) was calculated.Protein expression of PGC-1α, (involved in the regulation of mitochondrial biogenesis),COXIV,COXI(marker of mitochondrial biogenesis),fis-1(involved in mitochondrial fission),mfn-2(involved in mitochondrial fusion) were measured with western blot.Histological studies were performed with the stain methods of HE and Masson’s trichrome.Ultra structure of non-infarcted left-ventricular tissue and skeletal muscle were studied with electron micrograph.Results:1.There is no difference in theLVIDs,LVIDd,EF,CO,PGC-1α, COXIV,COXI expression between sham+E group and sham group.R3,RCR,fis-1, mfn-2 protein expression were higher in sham+E group compared with sham group. 2.Compared with sham group,MI group had higher R4,lower RCR,higher LVIDs, LVIDd,lower EF,CO,higher COXIV,COXI,fis-1 expression,lower mfn-2 expression,higher mitochondrial volume.3.Compared with MI group,MI+E group had higherLVIDs,LVIDd,CO,HR,lower EF,higher R4,RCR,higher COXIV, COXI protein expression,lower fis-1,mfn-2 expression,higher mitochondrial volume. Conclusions:1.Aerobic exercise training enhanced the mitochondrial function and proliferation in the myocardium and skeletal muscle of rats post myocardial infarction.Aerobic exercise training may have a favorable effect on the rats post myocardial infarction.2.Moderate aerobic exercise can not elevate the cardiac function at rest of the normal rats,can not enhance the mitochondrial biogenesis of cardiac muscle for normal rats.But aerobic exercise training enhanced the mitochondrial function and dynamics.3.After myocardial infarction,the cardiac muscle mitochondria function were impaired,mitochondrial proliferation were triggered,mitochondrial mitochondria dynamics balance was impaired, mitochondrial fission was elevated and fusion was depressed.4.Mitochondrial functional status instead of mitochondrial biogenesis participates the adaptation of cardiac muscle to aerobic training in the early stage.5.Mitochondrial dynamics may play an important role in the regulation of mitochondrial function status.6.Cardiac remodeling post myocardial infarction may be relevant to cardiac muscle mitochondrial biogenesis.