Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model.

AIMS: Exercise training (ET) has a cardioprotective effect and can alter the molecular response to myocardial infarction (MI). The Neuregulin 1 (NRG1)/ErbB signaling plays a critical role in cardiac repair and regeneration in the failing heart. We sought to investigate whether ET following MI could activate the NRG1/ErbB signaling and promote cardiac repair and regeneration. MAIN METHODS: Male Sprague-Dawley rats were used to establish the MI model. Exercise-trained animals were subjected to four weeks of exercise (16m/min, 50min/d, 5d/wk) following the surgery. AG1478 was used as an inhibitor of ErbB (1mg/kg body weight, administered i.v. every other day during the process of training). NRG1/ErbB signaling activation, cardiomyocyte (CM) proliferation and apoptosis were evaluated. KEY FINDINGS: In the exercise-trained rats, NRG1 expression was up-regulated and ErbB/PI3K/Akt signaling was activated compared with the MI group. In addition, ET preserved heart function accompanied with increased numbers of BrdU(+) CMs, PCNA(+) CMs and c-kit(+) cells, and reduced apoptosis level in the MI rats. In contrast, blocking ErbB signaling by AG1478 attenuated the ET-induced cardiac repair and regeneration. SIGNIFICANCE: ET up-regulates NRG1 expression and activates ErbB2, ErbB4 and PI3K/Akt signal transduction to promote cardiac repair through endogenous regeneration. Activation of ErbB may be an underlying mechanism for the ET-induced cardiac repair and regeneration following MI.

[Research advance on cardiomyocyte proliferation induced by aerobic exercise and stem cell mobilization].

Appropriate exercise is the effective way for the prevention and treatment of heart diseases. Its mechanism has not been completely elucidated, and the safe and effective exercise prescription needs to be studied systematically. Exercises give rise to secretion of various cell factors, effective stem cell mobilization, physiological hypertrophy and differentiation and proliferation of cardiomyocytes. The cell sources of adult cardiomyocyte proliferation included viable cardiomyocytes, cardiac stem/progenitor cells, bone marrow stem cells, peripheral stem cells. Stem cell mobilization, homing and differentiation are the cellular basis of myocardial repair after injury. From the potential of cardiomyocyte proliferation, stem cell therapy after myocardial infarction and cardiac myocyte proliferation induced by exercise, this review focused on the stem cells mobilization promoted by aerobic exercise, the possible mechanism of cardiac repair and functional amelioration induced by the differentiation of those stem cells after myocardial infarction, the problems remained to be further studied and correlative research progress.

Aerobic exercise inhibits sympathetic nerve sprouting and restores ß-adrenergic receptor balance in rats with myocardial infarction.

BACKGROUND: Cardiac sympathetic nerve sprouting and the dysregulation of ß-adrenergic receptor (ß-AR) play a critical role in the deterioration of cardiac function after myocardial infarction (MI). Growing evidence indicates that exercise provides protection against MI. The aims of this study were to investigate whether aerobic exercise following MI could inhibit sympathetic nerve sprouting and restore the balance of ß3-AR/ß1-AR. METHODS: Male Sprague-Dawley rats were divided into three groups: sham-operated control group (SC), MI group (MI), and MI with aerobic exercise group (ME). The rats in ME group were assigned to 8 weeks of exercise protocol (16 m/min, 50 min/d, 5 d/wk). The expression of nerve growth factor (NGF), the sympathetic nerve marker-tyrosine hydroxylase (TH), the nerve sprouting marker-growth associated protein 43 (GAP43), and ß1- and ß2-AR expression in the peri-infarct area of the left ventricle (LV) were measured by Western blot and immunohistochemistry, while ß3-AR expression was determined by Western blot and immunofluorescence. Endothelial nitric oxide synthase (NOS2), phospho-NOS2 (p-NOS2), and neuronal nitric oxide synthase (NOS1) were measured by Western blot. RESULTS: MI increased LV end-diastolic pressure (LVEDP), and decreased LV systolic pressure (LVSP). Compared with the MI group, aerobic exercise significantly decreased LVEDP and increased LVSP. The protein expression of TH, GAP43 and NGF was significantly increased after MI, which was normalized by exercise. Compared with the SC group, the ratios of ß2-AR/ß1-AR and ß3-AR/ß1-AR were elevated in the MI group, and the protein expression of ß3-AR and NOS1 increased after MI. Compared with the MI group, the ratios of ß2-AR/ß1-AR and ß3-AR/ß1-AR were normalized in the ME group, while the protein expression of ß3-AR and NOS1 significantly increased, and NOS2 was activated by exercise. CONCLUSIONS: Aerobic exercise inhibits cardiac sympathetic nerve sprouting, restores ß3-AR/ß1-AR balance and increases ß3-AR expression through the activation of NOS2 and NOS1 after myocardial infarction.

[Exercise intervention in skeletal muscle endocrine function].

As a new secretory organ skeletal muscle, which could secrete a variety of biological active substances, plays an important role in biological function and clinical medicine, and has important research value and application scenarios in the field of sports medicine. Different mode and intensity of exercise would give different influences on skeletal muscle endocrine function. Exercise intervention could improve the chronic disease, such as metabolic disease (obesity, diabetes) and muscle atrophy by changing endocrine function of the skeletal muscle. It will be great valuable to explore the mechanisms of exercise-induced skeletal muscle endocrine, seek for the appropriate biomarker, make exercise prescription, which would give improtant theoretical value and application prospect for the exercise system function improvement metabolic disease grevention and exercise rehabilitation of the systemic diseases.