The effect of prolonged physical training and high fat diet on heart size and body weight in rats

White male Woodlyn Wistar rats (aged 9-10 weeks) were subjected to prolonged physical training on a treadmill for 10 weeks. After 4 weeks half of the rats received a high fat test diet (45%) (Nutritional Biochemical Corporation) while the control group was fed standard lab chow (Purina lab chow). The body weights, heart weights, and heart weight per 100 g body weight were compared in a two by two factorial analysis, the independent variables being condition (exercise or sedentary) and diet (balanced or high fat). After 10 weeks the difference in body weight between the sedentary rats (body weight (BW) equals 514.4 plus or minus 76.4 g) and the exercise rats (BW equals 389 plus or minus 44 g) was significant (p less than 0.05). The difference in body weight between the high fat diet rats (BW equals 479 plus or minus 80 g, n equals 10) and the balanced diet group (BW equals 424 plus or minus 76 g, n equals 10) was also significant (p less than 0.05). No significant differences were observed in heart weight among any of the groups whereas a significant difference was noted between the sedentary group and the exercise group with respect to heart weight : body weight ratio. Thus the exercise rats had relatively larger hearts than the sedentary group (p less than 0.05) but no evidence for cardiac hypertrophy in the exercise group compared with the sedentary group ws observed. The difference with regard to heart ratios between the balanced diet and high fat diet groups was not significant and no interaction was present (p equals 0.065). It was concluded that cardiac hypertrophy is not necessarily a consequence of prolonged physical training but is a product of the type of training, the intensity and duration, and the emotional stress involved. Prolonged physical exercise was a powerful deterrent to weight gain even in rats on a high fat diet. In the absence of the development of cardiac hypertrophy in response to prolonged training, further work is needed to quantify the factors that result in cardiac hypertrophy and to identify other changes that may be occurring in the cardiovascular system in response to prolonged physical training.     

Grape polyphenols and exercise training have distinct molecular effects on cardiac hypertrophy in a model of obese insulin-resistant rats

Obesity and exercise lead to structural changes in heart such as cardiac hypertrophy. The underlying signaling pathways vary according to the source of the overload, be it physiological (exercise) or pathologic (obesity). The physiological pathway relies more on PI3K-Akt signaling while the pathologic pathway involves calcineurin-Nuclear factor of activated T-cells activation and fibrosis accumulation. Independently, exercise and polyphenols have demonstrated to prevent pathologic cardiac hypertrophy. Therefore, we investigated the molecular adaptations of the combination of exercise training and grape polyphenols supplementation (EXOPP) in obese high-fat fed rats on heart adaptation in comparison to exercise (EXO), polyphenols supplementation (PP) and high-fat fed rats (HF), alone. Exercised and PP rats presented a higher heart weight/body weight ratio compared to HF rats. EXO and EXOPP depicted an increase in cell-surface area, P-Akt/Akt, P-AMPK/AMPK ratios with a decreased fibrosis and calcineurin expression, illustrating an activation of the physiological pathway, but no additional benefit of the combination. In contrast, neither cell-surface area nor Akt signaling increased in PP rats; but markedly decreased fibrosis, calcineurin expression, systolic blood pressure, higher SERCA and P-Phospholamdan/Phospholamdan levels were observed. These data suggest that PP rats have a shift from pathologic toward physiological hypertrophy. Our study demonstrates that polyphenols supplementation has physical-activity-status-specific effects; it appears to be more protective in sedentary obese insulin-resistant rats than in the exercised ones. Exercise training improved metabolic and cardiac alterations without a synergistic effect of polyphenols supplementation. These data highlight a greater effect of exercise than polyphenols supplementation for the treatment of cardiac alterations in obese insulin-resistant rats.     

Training-induced bradycardia and intrinsic heart rate in rats

After 10 weeks of treadmill training, female Sprague-Dawley rats had developed a bradycardia at exercise on submaximal work loads. This bradycardia was also present after autonomic denervation and in isolated perfused heart preparations. The heart weight/body weight ratio was increased in these trained animals compared to untrained littermates. Sympathectomized, trained rats developed the same degree of cardiac hypertrophy, but their heart rate after denervation and in the isolated heart was the same as in sympathectomized, untrained rats. It is concluded that the bradycardia of trained and thereafter denervated animals seen in this and a previous investigation represents an adaptation within the heart itself, since it was present in the isolated heart. These results thus provide further evidence for a non-neural component in training-induced bradycardia. Since the trained sympathectomized rats had a cardiac hypertrophy but no reduction of intrinsic heart rate, it seems likely that the myocardial mass is of minor importance for the level of intrinsic heart rate.     

科素亚对长期大强度运动所致大鼠心脏纤维化的预防作用

目的:研究血管紧张素Ⅱ1型受体拮抗剂科素亚对长期大强度运动所致心脏纤维化的预防作用。方法:48只雄性Wistar大鼠随机分为4组:对照组,科素亚处理的对照组,运动组,运动+科素亚处理组。运动组大鼠给予16周大强度运动,科素亚处理的大鼠每天训练前口服科素亚每次(50毫克/公斤/天)。通过计算心系数和观察心脏的组织形态学评估和比较各组大鼠心脏肥大的程度,免疫印迹法检测和比较各组大鼠4个心腔内转化生长因子-β1、纤维连接蛋白1、基质金属蛋白酶-2、I型胶原蛋白和III型胶原蛋白的蛋白表达水平。结果:长期大强度运动可造成大鼠左心室心脏壁肥大和右心室胶原沉积,心房和右心室的主要纤维化生物标志物的蛋白表达水平显著增加。科素亚预处理能够减少主要纤维化生物标志物TGF-β1、FIBROECTIN-1、MMP-2、TIMP-1、COLLAGEN-I、COLLAGEN-III表达水平,但不能完全改变心脏重量与体重比值增大的状态。结论:科素亚可部分预防耐力运动训练所致的心脏纤维化,但不能彻底改善心脏肥大。     

Contrasting effect of exercise and angiotensin II hypertension on in vivo and in vitro cardiac angiogenesis in rats

Cardiac vessel density (beta-actin immunolabeling) and angiogenic capacity of coronary artery explants (culture in collagen gel) was determined in hypertrophied heart obtained by exercise training (10 wk) or ANG II infusion for 10 days. A group of rats received ANG II the last 10 days of training. The heart weight index was similarly elevated after exercise, and ANG II-hypertension compared with controls (3.16 +/- 0.09 and 3.11 +/- 0.11 vs. 2.68 +/- 0.08 mg/g, respectively), whereas tail cuff pressure (TCP) increased only in sedentary rats infused with ANG II. Vessel density was increased by 36% in trained rats and reduced by 30% in ANG II-infused rats. The number of sprouts generated by coronary rings was reduced by 50% in ANG II-infused rats and increased by 50% in exercise trained rats compared with controls (35 +/- 4 and 113 +/- 5 vs. 71 +/- 1 sprouts per ring, respectively). Exercise-training partly prevented the hypertensive effect of ANG II (TCP of 141 +/- 5 mmHg), whereas heart weight index (3.66 +/- 0.06 mg/g body wt) was not lowered. Myocardial vessel density was normalized, and sprouting from coronary rings increased by 50% in trained rats infused with ANG II compared with sedentary normotensive rats. Cardiac VEGF (Western blot analysis) was higher in hypertensive rats and not affected by exercise. Facing a similar increase in cardiac mass, intense training, but not ANG II hypertension, is accompanied by an increase in vascular density of the heart. The effect of training is unlikely related to changes in resting VEGF and may represent enhanced angiogenic capacity of the coronary vascular bed.     

Time course alterations of myocardial endothelin-1 production during the formation of exercise training-induced cardiac hypertrophy

Endothelin (ET)-1 is produced by endothelial cells and cardiac myocytes. ET-1 has positive inotropic and chronotropic effects on the heart and causes myocardial cell hypertrophy. Exercise training induces a physiologic cardiac hypertrophy. To study whether myocardial ET-1 is involved in the formation of exercise training-induced cardiac hypertrophy, we investigated time-course alterations of myocardial ET-1 gene expression and ET-1 peptide level in the heart of rats during a formative process of exercise training-induced cardiac hypertrophy. We used the hearts of rats that had been exercise-trained for 4 weeks (4WT) or 8 weeks (8WT) and sedentary control rats for 4 weeks (4WC) or 8 weeks (8WC). Exercise-trained rats performed treadmill running for 5 days/week (60 mins/day). Left ventricular mass index and wall thickness and stroke volume index, measured using echocardiography, in the 8WT group were significantly greater than in the 8WC group, although there were no differences between the 4WC and 4WT groups in these parameters. These results indicated that the 8WT rats developed physiologic cardiac hypertrophy, whereas the 4WT rats did not yet have cardiac hypertrophy. Myocardial ET-1 gene expression and tissue ET-1 concentration in the heart were significantly higher in the 8WT group than in the 8WC group, whereas these values did not differ between the 4WC and 4WT groups. The present study suggests that an alternation of myocardial ET-1 production corresponds with the formation of exercise training-induced cardiac hypertrophy. Therefore, the exercise training-induced change in myocardial ET-1 production may participate in a mechanism of exercise training-induced cardiac adaptation (e.g., cardiac hypertrophy).     

Effect of short- and long-term strength exercise on cardiac oxidative stress and performance in rat

Increase in heart metabolism during severe exercise facilitates production of ROS and result in oxidative stress. Due to shortage of information, the effect of chronic strength exercise on oxidative stress and contractile function of the heart was assessed to explore the threshold for oxidative stress in this kind of exercise training. Male Wistar rats (80) were divided into two test groups exercised 1 and 3 months and two control groups without exercise. Strength exercise was carried by wearing a Canvas Jacket with weights and forced rats to lift the weights. Rats were exercised at 70% of maximum lifted weight 6 days/week, four times/day, and 12 repetitions each time. Finally, the hearts of ten rats/group were homogenized and MDA, SOD, GPX, and catalase (CAT) were determined by ELISA method. In other ten rats/group, left ventricle systolic and end diastolic pressures (LVSP and LVEDP) and contractility indices (LVDP and +dp/dt max) and relaxation velocity (−dp/dt max) were recorded. The coronary outflow was collected. Short- and long-term strength exercise increased heart weight and heart/BW ratio (P < 0.05). In the 3-month exercise group, basal heart rate decreased (P < 0.05). LVEDP did not change but LVDP, +dp/dt max, −dp/dt max, and coronary flow significantly increased in both exercise groups (P < 0.05). None of MDA or SOD, GPX, and CAT significantly changed. The results showed that sub-maximal chronic strength exercise improves heart efficiency without increase in oxidative stress index or decrease in antioxidant defense capacity. These imply that long-time strength exercise up to this intensity is safe for cardiac health.     

Effects of exercise training on papain-induced pulmonary emphysema in Wistar rats.

The purpose of the present study was to evaluate the role of exercise training on the development of papain-induced emphysema in rats. Our hypothesis was that the increase in pulmonary tissue stretching associated with exercise could increase the severity of a protease-induced emphysema. Wistar rats were randomly assigned to four groups (n = 10 for each group) that received, respectively, intratracheal infusion of papain (6 mg in 1 ml of 0.9% NaCl) or vehicle and were submitted or not to a protocol of exercise on a treadmill. Rats exercised at 13.3 m/min, 6 days/wk, for 9 wk (increasing exercise time, from 10 to 35 min). We measured respiratory system elastance and resistance, the size and weight of the heart, and pulmonary mean linear intercept (Lm). After 9 wk of exercise training, there were no differences in respiratory system resistance and elastance values among the four experimental groups. Volume of the heart was significantly greater in rats submitted to exercise training (P = 0.007) compared with sedentary rats due to increases in volumes of both right and left cardiac chambers. Lm was significantly greater in rats that received papain compared with saline-infused rats (P = 0.025). Surprisingly, this was true, even though there was no significant decrease in elastance, possibly due to connective tissue remodeling. However, Lm was significantly greater in papain + exercise rats compared with rats that received papain and were not submitted to exercise. We conclude that exercise training can increase alveolar damage induced by papain infusion.     

Changes in the rat heart proteome induced by exercise training: Increased abundance of heat shock protein hsp20

Chronic exercise training elicits adaptations in the heart that improve pump function and confer cardioprotection. To identify molecular mechanisms by which exercise training stimulates this favorable phenotype, a proteomic approach was employed to detect rat cardiac proteins that were differentially expressed or modified after exercise training. Exercise-trained rats underwent six weeks of progressive treadmill training five days/week, 0% grade, using an interval training protocol. Sedentary control rats were age- and weight-matched to the exercise-trained rats. Hearts were harvested at various times (0-72 h) after the last bout of exercise and were used to generate 2-D electrophoretic proteome maps and immunoblots. Compared with hearts of sedentary rats, 26 protein spot intensities were significantly altered in hypertrophied hearts of exercise-trained rats (p <0.05), and 12 spots appeared exclusively on gels from hearts of exercise-trained rats. Immunoblotting confirmed that chronic exercise training, but not a single bout of exercise, elicited a 2.5-fold increase in the abundance of one of the candidate proteins in the heart, a 20 kDa heat shock protein (hsp20) that persisted for at least 72 h of detraining. Thus, exercise training alters the cardiac proteome of the rat heart; the changes include a marked increase in the expression of hsp20.     

Exercise training increases the Ca(2+) sensitivity of tension in rat cardiac myocytes.

The heart is known to respond to a program of chronic exercise in ways that enhance cardiac function. However, the cellular mechanisms involved in training-induced improvements in the contractile function of the myocardium are not known. In this study we tested the hypothesis that increased contractility of the myocardium associated with exercise training is due, in part, to increases in the Ca(2+) sensitivity of steady-state tension. Female Sprague-Dawley rats were randomly divided into sedentary control (C) and exercise-trained (T) groups. The T rats underwent 11 wk of progressive treadmill exercise (1 h/day, 5 days/wk, 26 m/min, 20% grade). Evidence of training effect included a 5.9% increase in heart mass, increases in heart weight-to-body weight ratio, and a 60% increase in skeletal muscle citrate synthase activity in T rats compared with C rats. After the training program, cardiac myocytes were isolated from T and C hearts. Myocytes were chemically skinned (i.e., the sarcolemma was removed) and attached to a force transducer, and steady-state tension was determined in solutions of various Ca(2+) concentrations ([Ca(2+)]). Myocytes isolated from the hearts of T rats showed a significantly (P < 0.01) increased sensitivity of tension to [Ca(2+)]. The [Ca(2+)] giving 50% of maximal tension (pCa(50)) was 5.90 +/- 0.033 and 5.82 +/- 0.023 (SD) in T and C myocytes, respectively (n = 70 myocytes/group). This result suggests that exercise training affects the myofibrillar proteins, such that Ca(2+) sensitivity is increased, and that this may be the mechanism that underlies, at least in part, the effect of training to increase myocardial contractility.     

Myocardial Na+/H+ exchanger-1 (NHE1) content is decreased by exercise training

The effect of exercise training on myocardial Na⁺/H⁺ exchanger-1 (NHE1) protein expression was examined. Adult female Sprague–Dawley rats were randomly divided into sedentary (S; n?=?8) and exercised (E; n?=?9) groups. Twenty-four hours after the last exercise bout, hearts were weighed and connected to an isolated perfused working heart apparatus for evaluation of cardiac functional performance. Heart weight and heart weight/body weight from E rats was significantly increased by 7.1 and 7.2 % (P?<?0.05), respectively, compared with S hearts. The E hearts displayed 15 % greater cardiac output and 35 % external cardiac work compared with the S group at both low and high workloads (P?<?0.05 for both parameters). Left ventricular tissue from the same hearts was homogenized and NHE1 and Na⁺/Ca²⁺ exchanger (NCX) content determined by Western blotting. E hearts had a 38 % (P?<?0.001) reduction in NHE1 content related to S hearts, and there was no difference in NCX content between groups. Cytochrome c oxidase activity in plantaris increased by 100 % (P?<?0.05) and was assessed as a marker of mitochondria content and to verify training status. Our data indicate that exercise training at an intensity that results in cardiac hypertrophy and improved performance is accompanied by decreased NHE1 content in heart.     

Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts

Cardiac myocytes produce nitric oxide (NO). We studied the effects of intense exercise on the expression of NO synthase (NOS) and the tissue level of nitrite (NO(2)(-))/nitrate (NO(3)(-)) (i.e., NOx), which are stable end products of NO in the heart. Rats ran on a treadmill for 45 min. Immediately after this exercise, the heart was quickly removed. Control rats remained at rest during the same 45-min period. The mRNA level of endothelial NOS (eNOS) in the heart was markedly lower in the exercised rats than in the control rats. Western blot analysis confirmed downregulation of eNOS protein in the heart after exercise. Tissue NOx level in the heart was significantly lower in the exercised rats than in the control rats. The present study revealed for the first time that production of NO in the heart is decreased by intense exercise. Because NO attenuates positive inotropic and chronotropic responses to beta(1)-adrenergic stimulation in the heart, the decrease in cardiac production of NO by intense exercise may contribute to the acceleration of increase in myocardial contractility and heart rate during intense exercise.     

Exercise training and beta-blocker treatment ameliorate age-dependent impairment of beta-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation

Cardiac beta-adrenergic receptor (beta-AR) signaling and left ventricular (LV) responses to beta-AR stimulation are impaired with aging. It is shown that exercise and beta-AR blockade have a favorable effect on cardiac and vascular beta-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on beta-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise (12 wk treadmill training), metoprolol (250 mg.kg(-1).day(-1) for 4 wk), and exercise plus metoprolol treatment protocols. Ten male Wistar-Kyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprolol-treated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to beta-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane beta-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac beta-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-protein-receptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of beta-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and beta-AR blockade can similarly ameliorate beta-AR signaling in the aged heart, leading to improved beta-AR responsiveness and corresponding LV inotropic reserve.     

Activation pattern of MAPK signaling in the hearts of trained and untrained rats following a single bout of exercise.

Since exercise training causes cardiac hypertrophy and a single bout induces mechanical stress to the heart, the present study aimed to characterize the activation patterns of multiple MAPK signaling pathways in the heart after a single bout of exercise or chronic exercises. The hearts of untrained rats received 5, 15, and 30 min of treadmill running exercise (Ex5 to Ex30) and rested for 0.5, 1, 3, 6, 12, and 24 h (PostEx0.5 to PostEx24) before subjecting them to the following different experiments. Activation of MAPKs (ERK, JNK, and p38) and MAPKKs (MEK1/2, SEK, and MKK3/6) increased immediately after acute exercise in a time-dependent manner, with ERK, JNK, and p38 peaking at Ex15, Ex15, and Ex30, respectively. Expression of immediate early genes (c-fos, c-jun, and c-myc) was augmented and activator protein-1 DNA binding activity was enhanced in untrained rats immediately after a single bout of exercise. The elevated levels of MAPKs declined to the resting levels within 24 h after exercise. In another set of experiments, following 4, 8, and 12 wk of exercise training, the rats exhibited significant cardiac hypertrophy by week 12. Activation of MAPKs in the 4-wk-trained rats increased after a 30-min single bout of exercise but decreased in the 8-wk group. Finally, the activity of MAPKs signaling in the 12-wk-trained rats exposed to an acute bout of exercise was unaltered. We conclude that exercise induces the activation of multiple MAPK (ERK, JNK, and p38) pathways in the heart, an effect that gradually declines with the development of exercise-induced cardiac hypertrophy.     

Exercise Training Restores Cardiac Protein Quality Control in Heart Failure

Exercise training is a well-known coadjuvant in heart failure treatment; however, the molecular mechanisms underlying its beneficial effects remain elusive. Despite the primary cause, heart failure is often preceded by two distinct phenomena: mitochondria dysfunction and cytosolic protein quality control disruption. The objective of the study was to determine the contribution of exercise training in regulating cardiac mitochondria metabolism and cytosolic protein quality control in a post-myocardial infarction-induced heart failure (MI-HF) animal model. Our data demonstrated that isolated cardiac mitochondria from MI-HF rats displayed decreased oxygen consumption, reduced maximum calcium uptake and elevated H₂O₂ release. These changes were accompanied by exacerbated cardiac oxidative stress and proteasomal insufficiency. Declined proteasomal activity contributes to cardiac protein quality control disruption in our MI-HF model. Using cultured neonatal cardiomyocytes, we showed that either antimycin A or H₂O₂ resulted in inactivation of proteasomal peptidase activity, accumulation of oxidized proteins and cell death, recapitulating our in vivo model. Of interest, eight weeks of exercise training improved cardiac function, peak oxygen uptake and exercise tolerance in MI-HF rats. Moreover, exercise training restored mitochondrial oxygen consumption, increased Ca²⁺-induced permeability transition and reduced H₂O₂ release in MI-HF rats. These changes were followed by reduced oxidative stress and better cardiac protein quality control. Taken together, our findings uncover the potential contribution of mitochondrial dysfunction and cytosolic protein quality control disruption to heart failure and highlight the positive effects of exercise training in re-establishing cardiac mitochondrial physiology and protein quality control, reinforcing the importance of this intervention as a non-pharmacological tool for heart failure therapy.     

Influence of long-term beta receptor stimulation with prenalterol on intrinsic heart rate in rats

Previous studies have shown that the intrinsic heart rate (IHR) may undergo changes, e.g., decrease after long-term endurance training. The mechanism for this adaptation is not known. In this study, rats were subjected to long-term oral treatment with the beta receptor stimulating drug prenalterol. During the treatment period heart rates at rest and during submaximal exercise were measured. Heart rate after 30 min rest and also 2 min after exercise was higher in the treated animals, due to the beta stimulation. The treated rats had a significantly lower heart rate increase during exercise than untreated controls, consistent with a partial beta-blocking effect of the drug in states with a high endogenous sympathetic activity. Therefore, the animals were not trained but only exposed to the increased stimulation of cardiac beta receptors accomplished by the drug while at rest. After 25 weeks, prenalterol was withdrawn and the IHR was measured in situ after a denervation procedure. The treatment with prenalterol had not altered the IHR. Our previous results from training studies indicate that a heart rate increase above a certain level or the stimulation for a lower setting of the IHR as seen after endurance training. In this study chronic beta receptor stimulation with prenalterol did not influence the IHR, which supports that hypothesis.     

Effect of N-2-mercaptopropionyl glycine on exercise-induced cardiac adaptations

The purpose of this study was to test the hypothesis that exercise-induced cardiac adaptations would be attenuated by the free radical scavenger N-2-mercaptopropionyl glycine (MPG). Male Sprague-Dawley rats were divided into four groups (n = 9-13 per group) for 3-4 wk: sedentary (S), S+MPG (100 mg/kg ip daily), exercised on a treadmill (E) (60 min/day, 5 days/wk, at a speed of 20 m/min up a 6° grade in a 6°C room), or E+MPG given 10 min prior to exercise. Additional rats (n = 55) were used to determine acute exercise effects on myocardial redox state [nonprotein nonglutathione sulfhydryls (NPNGSH)] and PI3K/Akt signaling pathway activation. Compared with S, NPNGSH levels were 48% lower in E (P < 0.05) and unchanged in E+MPG (P > 0.05). MPG also attenuated exercise-induced activation of the signaling proteins Akt and S6. Hearts from the 4-wk groups were weighed, and cardiac function was evaluated using an isolated perfused working heart preparation. Similar increases (P < 0.05) in both exercised groups were observed for heart weight and heart weight-to-body weight ratio. Cardiac function improved in E vs. S, as indicated by greater (P < 0.05) external work performed (cardiac output × systolic pressure) and efficiency of external work (work/Vo(2)). MPG prevented these exercise-induced functional improvements. Skeletal muscle mitochondria content increased to similar levels in E and E+MPG. This study provides evidence that free radicals do not play an essential role in the development of exercise-induced cardiac hypertrophy; however, they appear to be involved in functional cardiac adaptations, which may be mediated through the PI3K/Akt pathway.     

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.