Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart (original) (raw)
Related papers
2008
Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated b-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 + 5%), increased LV end diastolic pressure (20.9 + 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac b-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.
Cardiovascular Research, 2008
Aims We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated b-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Methods and results Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 + 5%), increased LV end diastolic pressure (20.9 + 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac b-adrenergic receptor downregulation and desensitization. Conclusions Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.
The Effect of Interval Training on Cardiac Angiogenesis Capacity in Rats with Myocardial Infarction
2019
Introduction: Myocardial infarction (MI) is the destruction and permanent and irreversible cell death of part of the cardiac muscle (myocardium) which occurs due to loss of blood flow to the heart. The condition disrupts individuals’ daily life and limits their performance. Evidence indicates the likely effect of exercise on increasing the capillary density of skeletal muscle and myocardium. Vascular endothelial growth factor (VEGF) and endostatin as well as their common receptors (Flt-1) are the most important factors involved in angiogenesis. Therefore, this research aimed to evaluate the effect of 6 weeks of interval training on the VEGF, Flt-1 and collagen 18 in rats with MI. Methods: 12 male Wistar rats with mean age of 10weeks and average weight of 250300 gr were infected with myocardial infarction and were assigned into two groups of (1) experimental (60 minutes of interval running on treadmill, each interval 4 minutes with the 6075 percent of Vo2max and 2 minutes of active r...
Histochemistry and Cell Biology, 2008
Enhanced angiogenesis, or capillary growth, has a prominent role among the various beneWcial eVects of exercise training on the myocardium. The aim of the present study is to assess if training-induced increases in capillarity and vascularization persist after 4 weeks of detraining. Adult male rats were trained to run on a treadmill for 10 weeks at »60% VO 2max , which did not induce cardiac hypertrophy, but increased (P < 0.05) the soleus/ body weight ratio, left ventricle capillarity and von Willebrand-positive cell density (n = 6). In another group of animals (n = 6) subjected to training followed by 4-week detraining, the soleus/body weight ratio returned to normal, with only partial reversal of left ventricle capillarity and von Willebrand-positive cell density. Markers of angiogenesis (VEGF, KDR/VEGF-R2 and HIF-1 mRNA, studied by real-time RT-PCR) were upregulated at the end of training, and returned to baseline value after detraining. Electron microscopy highlighted some morphological features in trained hearts (endothelial cell sprouting and bridges and pericyte detachment), suggestive of endothelial cell proliferation and capillary growth that were absent in untrained and detrained hearts. We conclude that the training-induced increase in cardiac capillarity and vascularization are retained for some time upon cessation of the training program even in the absence of angiogenic stimuli.
Basic Research in Cardiology, 2010
Alterations in circulating angiogenic cells (CAC) and endothelial progenitor cells (EPC), known to contribute to endothelial repair, could explain the reversal of endothelial function in response to exercise training. Moreover, training-induced vascular remodeling might affect the acute response of EPC and CAC following a single exercise bout. We studied the impact of exercise training on CAC function and numbers of CD34 ? /KDR ? EPC in patients with chronic heart failure (CHF) and we assessed the effect of acute exercise on CAC and EPC in sedentary and trained patients. Twenty-one sedentary CHF patients underwent 6-month exercise training and were compared to a non-trained control group (n = 17) and 10 healthy age-matched subjects. At baseline and follow-up, flow-mediated dilation was assessed and graded exercise testing (GXT) was performed. Before and immediately after GXT, CAC migratory capacity was assessed in vitro and circulating CD34 ? /KDR ? EPC were quantified using flow cytometry. At baseline, CAC migration was significantly impaired in sedentary CHF patients but normalized acutely after GXT. Training corrected endothelial dysfunction, which coincided with a 77% increase in CAC migration (P = 0.0001). Moreover, the GXT-induced improvement detected at baseline was no longer observed after training. Numbers of CD34 ? /KDR ? EPC increased following 6-month exercise training (P = 0.021), but were not affected by GXT, either prior or post-training. In conclusion, the present findings demonstrate for the first time that exercise training in CHF reverses CAC dysfunction and increases numbers of CD34 ? /KDR ? EPC, which is accompanied by improvement of peripheral endothelial function. The acute exercise-induced changes in CAC function wane with exercise training, suggesting that repetitive exercise bouts progressively lead to functional endothelial repair.
Circulation Research, 2007
The extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca 2ϩ -handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary exercise, started early after a large MI, on left ventricular (LV) remodeling and dysfunction in the mouse. Exercise had no effect on survival, MI size or LV dimensions, but improved LV fractional shortening from 8Ϯ1 to 12Ϯ1%, and LVdP/dt P30 from 5295Ϯ207 to 5794Ϯ207 mm Hg/s (both PϽ0.05), and reduced pulmonary congestion. These global effects of exercise were associated with normalization of the MI-induced increase in myofilament Ca 2ϩ -sensitivity (⌬pCa 50 ϭ0.037). This effect of exercise was PKA-mediated and likely because of improved  1 -adrenergic signaling, as suggested by the increased  1 -adrenoceptor protein (48%) and cAMP levels (36%; all PϽ0.05). Exercise prevented the MI-induced decreased maximum force generating capacity of skinned cardiomyocytes (F max increased from 14.3Ϯ0.7 to 18.3Ϯ0.8 kN/m 2 PϽ0.05), which was associated with enhanced shortening of unloaded intact cardiomyocytes (from 4.1Ϯ0.3 to 7.0Ϯ0.6%; PϽ0.05). Furthermore, exercise reduced diastolic Ca 2ϩ -concentrations (by ϳ30%, PϽ0.05) despite the unchanged SERCA2a and PLB expression and PLB phosphorylation status. Importantly, exercise had no effect on Ca 2ϩ -transient amplitude, indicating that the improved LV and cardiomyocyte shortening were principally because of improved myofilament function. In conclusion, early exercise in mice after a large MI has no effect on LV remodeling, but attenuates global LV dysfunction. The latter can be explained by the exercise-induced improvement of myofilament function.
International Journal of Cardiology, 2012
We studied the effect of a short-term (3 weeks) exercise training program on the number of circulating CD34/KDR + endothelial progenitor cells (EPCs) and on serum levels of matrix metalloproteinases (MMPs) in chronic heart failure (CHF) patients as well as on serum capacity to foster colony forming unitsendothelial cells (CFU-ECs) in vitro. Methods: Effectiveness of training was assessed by the 6-minute walking test (6MWT). Peripheral blood and serum were obtained from fourteen patients with CHF due to coronary artery disease before and after an inpatient aerobic exercise training program. At admission and at discharge we analysed circulating EPC number and serum levels of MMPs, TIMP-1 and TNF-α. The number and function of CFU-EC colonies were evaluated in cultures performed with serum obtained before and after training. Results: After training, distance walked at 6MWT and number of circulating CD34/KDR + cells increased (from 154 ± 27 to 233 ± 48 m; P b 0.0001 and from 5 ± 3 to 9 ± 6 cells/ml P b 0.05, respectively). Conversely, serum concentrations of MMP-1 and TIMP-1 decreased significantly (from 11.4 ± 2.4 to 6.3 ± 1.1 ng/ml, and from 320.4 ± 41.2 to 167.2 ± 12.6 ng/ml, respectively, both P b 0.01), while MMP2/TIMP-1 and MMP-9/TIMP-1 ratios increased. Interestingly, we found increased CFU-EC proliferation in cultures performed with serum obtained after training. Conclusions: Considering that both EPCs and MMPs might play a role in vascular remodeling, the increased number of EPCs and MMP activities observed in this study, suggest that the selected short-term exercise training could be a potential therapeutic strategy to rescue cardiac function in CHF patients.
Partial persistence of exercise induced myocardial angiogenesis
Enhanced angiogenesis, or capillary growth, has a prominent role among the various beneWcial eVects of exercise training on the myocardium. The aim of the present study is to assess if training-induced increases in capillarity and vascularization persist after 4 weeks of detraining. Adult male rats were trained to run on a treadmill for 10 weeks at »60% VO 2max , which did not induce cardiac hypertrophy, but increased (P < 0.05) the soleus/ body weight ratio, left ventricle capillarity and von Willebrand-positive cell density (n = 6). In another group of animals (n = 6) subjected to training followed by 4-week detraining, the soleus/body weight ratio returned to normal, with only partial reversal of left ventricle capillarity and von Willebrand-positive cell density. Markers of angiogenesis (VEGF, KDR/VEGF-R2 and HIF-1 mRNA, studied by real-time RT-PCR) were upregulated at the end of training, and returned to baseline value after detraining. Electron microscopy highlighted some morphological features in trained hearts (endothelial cell sprouting and bridges and pericyte detachment), suggestive of endothelial cell proliferation and capillary growth that were absent in untrained and detrained hearts. We conclude that the training-induced increase in cardiac capillarity and vascularization are retained for some time upon cessation of the training program even in the absence of angiogenic stimuli.
Journal of Cellular and Molecular Medicine, 2018
We evaluated the influence of aerobic exercise on cardiac remodelling during the transition from compensated left ventricular (LV) hypertrophy to clinical heart failure in aortic stenosis (AS) rats. Eighteen weeks after AS induction, rats were assigned into sedentary (AS) and exercised (AS-Ex) groups. Results were compared to Sham rats. Exercise was performed on treadmill for 8 weeks. Exercise improved functional capacity. Echocardiogram showed no differences between AS-Ex and AS groups. After exercise, fractional shortening and ejection fraction were lower in AS-Ex than Sham. Myocyte diameter and interstitial collagen fraction were higher in AS and AS-Ex than Sham; however, myocyte diameter was higher in AS-Ex than AS. Myocardial oxidative stress, evaluated by lipid hydroperoxide concentration, was higher in AS than Sham and was normalized by exercise. Gene expression of the NADPH oxidase subunits NOX2 and NOX4, which participate in ROS generation, did not differ between groups. Activity of the antioxidant enzyme superoxide dismutase was lower in AS and AS-Ex than Sham and glutathione peroxidase was lower in AS-Ex than Sham. Total and reduced myocardial glutathione, which is involved in cellular defence against oxidative stress, was lower in AS than Sham and total glutathione was higher in AS-Ex than AS. The MAPK JNK was higher in AS-Ex than Sham and AS groups. Phosphorylated P38 was lower in AS-Ex than AS. Despite improving functional capacity, aerobic exercise does not change LV function in AS rats. Exercise restores myocardial glutathione, reduces oxidative stress, impairs JNK signalling and further induces myocyte hypertrophy.