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Cardiovascular Research Advance Access originally published online on December 18, 2007
Cardiovascular Research 2008 78(2):385-394; doi:10.1093/cvr/cvm109
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

Exercise promotes angiogenesis and improves β-adrenergic receptor signalling in the post-ischaemic failing rat heart

Dario Leosco1,*,{dagger}, Giuseppe Rengo2,3,{dagger}, Guido Iaccarino1, Luca Golino1, Massimo Marchese1, Francesca Fortunato1, Carmela Zincarelli1,2, Emma Sanzari1, Michele Ciccarelli1,2, Gennaro Galasso1, Giovanna Giuseppina Altobelli4, Valeria Conti5, Gianfranco Matrone1, Vincenzo Cimini4, Nicola Ferrara3,6, Amelia Filippelli5, Walter J. Koch2 and Franco Rengo1,3

1 Cattedra di Geriatria, Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Università Federico II, Via Pansini 5, 80131 Napoli, Italy
2 Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA
3 Fondazione S. Maugeri—IRCCS, Telese, Italy
4 Dipartimento di Scienze Biomorfologiche e Funzionali, Università Federico II, Napoli, Italy
5 Dipartimento di Medicina Sperimentale e Centro di Eccellenza delle Malattie Cardiovascolari, 2^ Università di Napoli, Napoli, Italy
6 Dipartimento di Scienze della Salute, Università del Molise, Campobasso, Italy

* Corresponding author. Tel: +39 081 7462267; fax: +39 081 7462339. E-mail address: dleosco{at}unina.it

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.

KEYWORDS Heart failure; Exercise training; Angiogenesis; Vascular endothelial growth factor; β-adrenergic receptor

Time for primary review: 27 days

{dagger} Dario Leosco and Giuseppe Rengo were co-first authors of this work.


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