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

Dario Leosco, Giuseppe Rengo, Guido Iaccarino, Luca Golino, Massimo Marchese, Francesca Fortunato, Carmela Zincarelli, Emma Sanzari, Michele Ciccarelli, Gennaro Galasso, Giovanna Giuseppina Altobelli, Valeria Conti, Gianfranco Matrone, Vincenzo Cimini, Nicola Ferrara, Amelia Filippelli, Walter J. Koch, Franco Rengo

Research output: Contribution to journalArticle

99 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)385-394
Number of pages10
JournalCardiovascular Research
Volume78
Issue number2
DOIs
StatePublished - May 2008

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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