Role of exercise in the heart

Several studies suggested that regular phsysical exercise able to improve cardiovascular functions. This effect is not only preventing in healthy subjects, but also affects elder people and those with risk factors for cardiovascular diseases. Furthermore, exercise also seems to improve cardiac parameters in patients with cardiovascular diseases, such as hypertension, metabolic syndrome, myocardial infarction and heart failur. In primary and secondary prevention of cardiovascular diseases, exercise seems to be important, by reducing cardiovascular risk factors, including obesity, hyperglycaemia, high blood pressure and systemic inflammation decreased significantly. In treatment by exercise, important factors are activity, frequency, duration and intensity, which determined by the patient’s fitness level, personal goals and medical conditions. There are several types of exercise, which improves cardiac functions, such as resistance exercise, strength training, flexibility and streching exercises and balance exercise. From this aspect, walking, jogging, swimming, treadmill, exercise with the patient’s own weight or use hand weights, and streching, which contribute to improve motor control and muscle strength, are beneficial. In the creating of exercise programs for patients suffers from cardiovascular diseases, it is suggested to maximaze the type of exercises spread in a week, depends on the patients fitness, and medical conditions.

The molecular mechanism of the benefits of exercise is described by several authors. Physical exercise seems to decrease ROS production and oxidative stress, by improve the antioxidant system in the myocardium. The major antioxidant enzymes in the myocardium, are superoxide dismutase (SOD), gluthation peroxidase (GSHPx), and catalase. Rinaldi et al. showed that in exercise-trained old rats, there is an increasing expression can be observed in both two forms of SOD, the manganase SOD (MnSOD) and copper/zinc SOD. However, it appears, that increased expression of MnSOD can triggered by high intensity of exercise. It is described, that MnSOD is essential for the protective effect of exercise in myocardial infarction. Changes in metabolism and protein expression in cardiac mitochondria also contributes to beneficial effects of exercise. In exercise trained rats, Starnes et al. proved that a decreased ROS production could observed in their experimental conditions in mitochodria. In addition, the downregulation of monoamine-oxidase-A also induced by exercise, may protect from ischemia/reperfusion-induced myocardial damage, proved by Pchejetski et al. in monoamine-oxidase-A knockout mice. It is also measurable, that exercise induce a decrease in Ca²⁺ concentration in mitochondria, which contribute to the superssion of calcium-induced opening of mitochondria transition pore, it has a proapoptotic effect. There is also demonstrated, that exercise able to decrease Ca²⁺, in a pathway which promote shorter action potential, thereby opening cardiomyocite sarcolemmal ATP sensitive K⁺ channel and cause myocyte repolarization, which contribute to the reduced opening rates of L-type Ca²⁺ channel, and thus a decreased Ca²⁺ level. Furthermore, exercise seems to protective against apoptosis, through change proapoptotic and antiapoptotic gene expression.

Exercise also impacts endothelial function. Among others, Hambrecht et al. and Kojda et al. have found that exercise training increase eNOS expression, thus NO production in the endothelium. Increased NO production occurs an increase in SOD expression through a positive feedback manner, wich increase the NO bioavailability itself, and reduces the degradation of NO to peroxynitrite, by ROS. NADPH oxidase contribute to the increased expression of eNOS, through generating ROS, especially O^2-, which forms H₂O₂ in a reaction catalyzed by SOD. The generating H₂O₂ is an effective activator of eNOS expression.

On-growing evidence demonstrate that there are important interaction between exercise and ROS generating NADPH oxidase expression and activity. Jenkins et al. found that in men with psychical inactivity shows increased expression of NADPH oxidase, thus oxidative stress. They also proved that acute and chronic exercise upreglate eNOS expression and able to supresses NADPH oxidase expression and activity. Hambrect et al. found that four-weeks of exercise enhance eNOS expression and phosphorylation of eNOS by an Akt-dependent manner, which is mediated by shear stress also observed. Furthermore, they found that exercise supresses ROS generation by reducing the expression of NADPH oxidase’s essential subunits, such as gp91phox, p22phox and Nox4. Several studies suggest that aerobic exercise change the oxidant-antioxidant balance, through decreasing ROS generating NADPH oxidases and ameliorate endothelial function. Touati et al. found that in high-fat diet-induced (HFD) obesity, exercise decreased atherosclerotic risk factors, without an importance to change HFD to a normal-fat diet. They also proved that exercise training or diet modification decreased Nox4 expression and activation, by inhibition the translocation of the p47phox subunit of NADPH oxidase. Furthermore, they described that protective effects of exercise related to increased expression and phosphorylation of eNOS in an Akt-dependent manner, decreased Nox activity and an increase in SOD-1 expression, which has an antioxidative and antiatherogenic effects. Lee et al. proved that in aging rat heart, regular modest intensity exercise decreased AT1R and Nox4 expression, which both putative regulators of TGF-Beta and effector of fibrosis, furthermore this has an antioxidant effect by decreasing Nox4.

Dillard et al. demonstrate for the first time, that exercise could lead to an increased lipid peroxidation, which may caused by the oxidative stress during exercise. Since then, several studies suggests the beneficial role of exercise in a long term period of training, and the fact that exercise lead to a highly stimulation of antioxidant system after the training. To reduce redox signaling during exercise, supplementation of antioxidants, alpha tocopherol and ascorbate (vitamin E and C) is seems to be promising. These vitamins able to decrease superoxide, NO, peroxynitrite, and H₂O₂ levels, thus contribute to reduce exercise-induced oxidative stress.

Miyachi et al. described that in heart failure rat model, a nine-week long exercise training significantly attenuate heart failure and facilitate cardiac anti-remodelling processes. Vitiello et al. demonstrated that prolonged strenuous exercise (PSE) in a motorized treadmill, seems to lead to cardiac dysfunction in rats. In humans prolonged strenuous exersice, such as marathon or triathlon, cause transient left ventricular (LV) dysfunction and increased myocardial cell damage.