1. Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart
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Vincenzo Cimini, Amelia Filippelli, Guido Iaccarino, Massimo Marchese, Gianfranco Matrone, Carmela Zincarelli, Gennaro Galasso, Luca Golino, Giuseppe Rengo, Francesca Fortunato, Nicola Ferrara, Emma Sanzari, Walter J. Koch, Michele Ciccarelli, Franco Rengo, Giovanna Giuseppina Altobelli, Dario Leosco, Valeria Conti, Leosco, D., Rengo, G., Iaccarino, G., Golino, L., Marchese, M., Fortunato, F., Zincarelli, C., Sanzari, E., Ciccarelli, M., Galasso, G., Altobelli, G. G., Conti, V., Matrone, G., Cimini, V., Ferrara, N., Filippelli, A., Koch, W. J., Rengo, F., Leosco, Dario, Ferrara, Nicola, and Rengo, Franco
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β-adrenergic receptor ,Male ,Vascular Endothelial Growth Factor A ,Time Factors ,Heart disease ,Physiology ,Left ,Wistar ,Myocardial Infarction ,Adrenergic ,Nitric Oxide Synthase Type II ,Adrenergic beta-Agonists ,pharmacology, Animals, Coronary Circulation, Coronary Vessels ,drug effects/metabolism/physiopathology, Disease Models ,Animal, Dose-Response Relationship ,Drug, Heart Failure ,etiology/metabolism/physiopathology/ultrasonography, Isoproterenol ,pharmacology, Male, Myocardial Contraction, Myocardial Infarction ,complications/metabolism/physiopathology/ultrasonography, Myocardium ,enzymology/metabolism/pathology, Neovascularization ,Physiologic ,drug effects, Nitric Oxide Synthase Type II ,metabolism, Nitric Oxide Synthase Type III, Physical Exertion, Proto-Oncogene Proteins c-akt ,metabolism, Rats, Rats ,Wistar, Receptors ,beta ,drug effects/metabolism, Signal Transduction ,drug effects, Time Factors, Vascular Endothelial Growth Factor A ,metabolism, Ventricular Function ,Left, Ventricular Remodeling ,Ventricular Function, Left ,Receptors ,Medicine ,Ventricular Function ,Coronary Vessel ,Adrenergic beta-Agonist ,Ultrasonography ,Ventricular Remodeling ,etiology/metabolism/physiopathology/ultrasonography ,enzymology/metabolism/pathology ,Coronary Vessels ,Angiogenesi ,medicine.anatomical_structure ,Drug ,Cardiology and Cardiovascular Medicine ,Signal Transduction ,medicine.medical_specialty ,drug effects/metabolism/physiopathology ,Time Factor ,Nitric Oxide Synthase Type III ,Physical Exertion ,Neovascularization, Physiologic ,Physical exercise ,complications/metabolism/physiopathology/ultrasonography ,Contractility ,Dose-Response Relationship ,Exercise training ,Coronary circulation ,Physiology (medical) ,Internal medicine ,Coronary Circulation ,Receptors, Adrenergic, beta ,Animals ,Rats, Wistar ,Ventricular remodeling ,Neovascularization ,Heart Failure ,Dose-Response Relationship, Drug ,business.industry ,Animal ,Myocardium ,Isoproterenol ,medicine.disease ,Myocardial Contraction ,Rats ,Disease Models, Animal ,Endocrinology ,Heart failure ,drug effects ,Disease Models ,Myocardial infarction complications ,Rat ,pharmacology ,Vascular endothelial growth factor ,business ,drug effects/metabolism ,metabolism ,Proto-Oncogene Proteins c-akt - Abstract
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 beta-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 beta-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.
- Published
- 2007
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