TY - JOUR
T1 - Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart
AU - Leosco, Dario
AU - Rengo, Giuseppe
AU - Iaccarino, Guido
AU - Golino, Luca
AU - Marchese, Massimo
AU - Fortunato, Francesca
AU - Zincarelli, Carmela
AU - Sanzari, Emma
AU - Ciccarelli, Michele
AU - Galasso, Gennaro
AU - Altobelli, Giovanna Giuseppina
AU - Conti, Valeria
AU - Matrone, Gianfranco
AU - Cimini, Vincenzo
AU - Ferrara, Nicola
AU - Filippelli, Amelia
AU - Koch, Walter J.
AU - Rengo, Franco
PY - 2008/5
Y1 - 2008/5
N2 - 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 β-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 β-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.
AB - 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 β-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 β-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.
KW - Angiogenesis
KW - Exercise training
KW - Heart failure
KW - Vascular endothelial growth factor
KW - β-adrenergic receptor
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U2 - 10.1093/cvr/cvm109
DO - 10.1093/cvr/cvm109
M3 - Article
C2 - 18093988
AN - SCOPUS:42349083039
VL - 78
SP - 385
EP - 394
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 2
ER -