Vascular endothelial growth factor blockade prevents the beneficial effects of β-blocker therapy on cardiac function, angiogenesis, and remodeling in heart failure

Giuseppe Rengo, Alessandro Cannavo, Daniela Liccardo, Carmela Zincarelli, Claudio De Lucia, Gennaro Pagano, Klara Komici, Valentina Parisi, Oriana Scala, Alessia Agresta, Antonio Rapacciuolo, Pasquale Perrone Filardi, Nicola Ferrara, Walter J. Koch, Bruno Trimarco, Grazia Daniela Femminella, Dario Leosco

Research output: Contribution to journalArticle

Abstract

BackgroundImpaired angiogenesis in the post-myocardial infarction heart contributes to the progression to heart failure. The inhibition of vascular endothelial growth factor (VEGF) signaling has been shown to be crucial for the transition from compensatory hypertrophy to cardiac failure. Importantly, â-adrenergic receptor blocker therapy has been also shown to improve myocardial perfusion by enhancing neoangiogenesis in the failing heart. Methods and ResultsEight weeks from surgically induced myocardial infarction, heart failure rats were randomized to receive bisoprolol (B) or vehicle. At the end of a 10-week treatment period, echocardiography revealed reduced cardiac diameters and improved cardiac function in B-treated compared with vehicle-treated rats. Moreover, B treatment was associated with increased cardiac angiogenesis and in vivo coronary perfusion and reduced cardiac fibrosis. Importantly, 2 weeks after B treatment was started, increased cardiac VEGF expression and Akt and endothelial NO synthase activation were observed by comparing B-treated with drug-untreated failing hearts. To test whether the proangiogenic effects of B act via activation of VEGF pathway, rats were intravenously injected with adenoviral vector encoding a decoy VEGF receptor (Ad-Flk) or a control adenovirus (Ad-C), at the start of the treatment with B. After 10 weeks, histological analysis revealed reduced capillary and coronary perfusion in B-treated plus Ad-Flk rats compared with B-treated plus Ad-C rats. Moreover, VEGF inhibition counteracted the positive effects of B on cardiac function and remodeling. Conclusionsâ-Blockade promotes cardiac angiogenesis in heart failure via activation of VEGF signaling pathway. â- Blocker induced enhancement of cardiac angiogenesis is essential for the favorable effects of this therapy on cardiac function and remodeling.

Original languageEnglish
Pages (from-to)1259-1267
Number of pages9
JournalCirculation: Heart Failure
Volume6
Issue number6
DOIs
Publication statusPublished - 2013

Keywords

  • Adrenergic β-1 receptor antagonists
  • Angiogenesis
  • Heart failure
  • Vascular endothelial growth factor A

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

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