Angiogenesis

, Volume 15, Issue 4, pp 581–592

Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice

  • Paolo E. Porporato
  • Valéry L. Payen
  • Christophe J. De Saedeleer
  • Véronique Préat
  • Jean-Paul Thissen
  • Olivier Feron
  • Pierre Sonveaux
Original Paper

DOI: 10.1007/s10456-012-9282-0

Cite this article as:
Porporato, P.E., Payen, V.L., De Saedeleer, C.J. et al. Angiogenesis (2012) 15: 581. doi:10.1007/s10456-012-9282-0

Abstract

Wounds notoriously accumulate lactate as a consequence of both anaerobic and aerobic glycolysis following microcirculation disruption, immune activation, and increased cell proliferation. Several pieces of evidence suggest that lactate actively participates in the healing process through the activation of several molecular pathways that collectively promote angiogenesis. Lactate indeed stimulates endothelial cell migration and tube formation in vitro, as well as the recruitment of circulating vascular progenitor cells and vascular morphogenesis in vivo. In this study, we examined whether the pro-angiogenic potential of lactate may be exploited therapeutically to accelerate wound healing. We show that lactate delivered from a Matrigel matrix improves reperfusion and opposes muscular atrophy in ischemic hindlimb wounds in mice. Both responses involve lactate-induced reparative angiogenesis. Using microdialysis and enzymatic measurements, we found that, contrary to poly-L-lactide (PLA), a subcutaneous implant of poly-D,L-lactide-co-glycolide (PLGA) allows sustained local and systemic lactate release. PLGA promoted angiogenesis and accelerated the closure of excisional skin wounds in different mouse strains. This polymer is FDA-approved for other applications, emphasizing the possibility of exploiting PLGA therapeutically to improve wound healing.

Keywords

Wound healing Ischemic wound Excisional wound Reparative angiogenesis Muscular atrophy Poly-D,L-lactide-co-glycolide (PLGA) 

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Paolo E. Porporato
    • 1
  • Valéry L. Payen
    • 1
  • Christophe J. De Saedeleer
    • 1
  • Véronique Préat
    • 2
  • Jean-Paul Thissen
    • 3
  • Olivier Feron
    • 1
  • Pierre Sonveaux
    • 1
  1. 1.Pole of PharmacologyUniversité catholique de Louvain (UCL)BrusselsBelgium
  2. 2.Department of Pharmaceutics and Drug Delivery, Louvain Drug Research InstituteUniversité catholique de Louvain (UCL)BrusselsBelgium
  3. 3.Pole of Endocrinology, Diabetology and NutritionUniversité catholique de Louvain (UCL)BrusselsBelgium

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