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The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling

Research output: Contribution to journalArticle

  • Federica Riu
  • Sadie C Slater
  • Eva Jover Garcia
  • Iker Rodriguez-Arabaolaza
  • Valeria Alvino
  • Elisa Avolio
  • Giuseppe Mangialardi
  • Andrea Cordaro
  • Simon Satchell
  • Carlo Zebele
  • Andrea Caporali
  • Gianni Angelini
  • Paolo Madeddu

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Original languageEnglish
Pages (from-to)5443
JournalScientific Reports
Issue number1
Early online date14 Jul 2017
Publication statusE-pub ahead of print - 14 Jul 2017


Transplantation of adventitial pericytes (APCs) improves recovery from tissue ischemia in preclinical animal models by still unknown mechanisms. This study investigates the role of the adipokine leptin (LEP) in the regulation of human APC biological functions. Transcriptomic analysis of APCs showed components of the LEP signalling pathway are modulated by hypoxia. Kinetic studies indicate cultured APCs release high amounts of immunoreactive LEP following exposure to hypoxia, continuing upon return to normoxia. Secreted LEP activates an autocrine/paracrine loop through binding to the LEP receptor (LEPR) and induction of STAT3 phosphorylation. Titration studies using recombinant LEP and siRNA knockdown of LEP or LEPR demonstrate the adipokine exerts important regulatory roles in APC growth, survival, migration and promotion of endothelial network formation. Heterogeneity in LEP expression and secretion may influence the reparative proficiency of APC therapy. Accordingly, the levels of LEP secretion predict the microvascular outcome of APCs transplantation in a mouse limb ischemia model. Moreover, we found that the expression of the Lepr gene is upregulated on resident vascular cells from murine ischemic muscles, thus providing a permissive milieu to transplanted LEP-expressing APCs. Results highlight a new mechanism responsible for APC adaptation to hypoxia and instrumental to vascular repair.

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