Cilostazol promotes angiogenesis after peripheral ischemia through a VEGF-dependent mechanism

Federico Biscetti, Giovanni Pecorini, Giuseppe Straface, Vincenzo Arena, Egidio Stigliano, Sergio Rutella, Franco Locatelli, Flavia Angelini, Giovanni Ghirlanda, Andrea Flex

Research output: Contribution to journalArticle

Abstract

Background/objectives: Cilostazol has been found to be effective for the treatment of intermittent claudication (IC). This compound has several beneficial effects on platelet aggregation, serum lipids and endothelial cells, but how these might relate to improvements in walking is not entirely understood. The aim of this work was to investigate the effects of cilostazol on angiogenic response in a murine model of peripheral ischemia and to clarify the underlying molecular mechanisms of that response. Methods: We studied ischemia-induced neovascularization in the ischemic hindlimb of cilostazol-treated and untreated control mice. Results: We found that the perfusion recovery was significantly improved in treated compared with control mice. Interestingly, there was a higher level of circulating endothelial progenitor cells (EPCs) in mice treated with cilostazol than in untreated mice. Furthermore, cilostazol administration resulted in upregulation of granulocyte colony-stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF) in the ischemic muscle of treated mice. Finally, inhibiting VEGF activity significantly reduced cilostazol-induced angiogenesis. Conclusions: The results of this study show that cilostazol administration enhances collateral blood flow in the ischemic hindlimbs of mice through a VEGF-dependent mechanism. These data may help to explain the beneficial effects that this drug has on patients with peripheral arterial disease (PAD) and IC.

Original languageEnglish
Pages (from-to)910-916
Number of pages7
JournalInternational Journal of Cardiology
Volume167
Issue number3
DOIs
Publication statusPublished - Aug 10 2013

Keywords

  • Angiogenesis
  • Cilostazol
  • Vascular endothelial growth factor
  • VEGF

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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