Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats.
Cardiac endoplasmic reticulum (ER) stress through accumulation of misfolded proteins plays a pivotal role in cardiovascular diseases. In an attempt to reestablish ER homoeostasis, the unfolded protein response (UPR) is activated. However, if ER stress persists, sustained UPR activation leads to apoptosis. There is no available therapy for ER stress relief. Considering that aerobic exercise training (AET) attenuates oxidative stress, mitochondrial dysfunction and calcium imbalance, it may be a potential strategy to reestablish cardiac ER homoeostasis. We test the hypothesis that AET would attenuate impaired cardiac ER stress after myocardial infarction (MI). Wistar rats underwent to either MI or sham surgeries. Four weeks later, rats underwent to 8 weeks of moderate-intensity AET. Myocardial infarction rats displayed cardiac dysfunction and lung oedema, suggesting heart failure. Cardiac dysfunction in MI rats was paralleled by increased protein levels of UPR markers (GRP78, DERLIN-1 and CHOP), accumulation of misfolded and polyubiquitinated proteins, and reduced chymotrypsin-like proteasome activity. These results suggest an impaired cardiac protein quality control. Aerobic exercise training improved exercise capacity and cardiac function of MI animals. Interestingly, AET blunted MI-induced ER stress by reducing protein levels of UPR markers, and accumulation of both misfolded and polyubiquinated proteins, which was associated with restored proteasome activity. Taken together, our study provide evidence for AET attenuation of ER stress through the reestablishment of cardiac protein quality control, which contributes to better cardiac function in post-MI heart failure rats. These results reinforce the importance of AET as primary non-pharmacological therapy to cardiovascular disease.
School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.|Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Luiz H M
LH
Bozi
School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
Paulo R
PR
Jannig
K.G. Jebsen Center of Exercise in Medicine at Department of Circulation and Medical Imaging, Norwegian University of Science and Technology - NTNU, Trondheim, Norway.
Natale
N
Rolim
School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
Vanessa A
VA
Voltarelli
Department of Pharmacology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil.
Paulo M M
PM
Dourado
K.G. Jebsen Center of Exercise in Medicine at Department of Circulation and Medical Imaging, Norwegian University of Science and Technology - NTNU, Trondheim, Norway.
Ulrik
U
Wisløff
School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil. pcbrum@usp.br.
Patricia C
PC
Brum
D000818:Animals; D059865:Endoplasmic Reticulum Stress; D006333:Heart Failure / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006334:Heart Function Tests; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D010805:Physical Conditioning, Animal; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism*; D017208:Rats, Wistar
D011506:Proteins
endoplasmic reticulum stress; exercise; myocardial infarction; protein quality control