Invited commentary

Abstract

The pathologic impairment of wound healing in ischemic and diabetic conditions could be normalized by poly-ADP-ribose polymerase (PARP) inhibition. Dr Zhou showed that PARP inhibition enhances neovascularization, including angiogenesis and endothelial progenitor cell mobilization. These studies suggest that PARP inhibition may represent a promising therapeutic strategy for wound healing and wound repair. However, these exciting studies raise some important questions. First of all, it would be interesting to determine whether the topical route of administration of PARP inhibitors would have similar improvement in wound healing as systemic delivery. Topical PARP inhibition treatment probably may not affect the bone marrow-derived endothelial progenitor cell mobilization and homing into the wound beds because of absence of or not enough PARP inhibitors in the circulation. Therefore, it will tell us the contribution of local angiogenesis and vasculogenesis in ischemic and diabetic wound healing by PARP inhibition. Second, it seems that there are conflicting results on regulation of angiogenesis by PARP in other pathologic conditions, such as cancer and retinal angiogenesis.1Tentori L. Lacal P.M. Muzi A. Dorio A.S. Leonetti C. Scarsella M. et al.Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis.Eur J Cancer. 2007; 43: 2124-2133Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 2Mao H. Lockyer P. Townley-Tilson W.H. Xie L. Pi X. LRP1 regulates retinal angiogenesis by inhibiting PARP-1 activity and endothelial cell proliferation.Arterioscler Thromb Vasc Biol. 2016; 36: 350-360Crossref PubMed Scopus (30) Google Scholar PARP inhibition was demonstrated to reduce angiogenesis by decreasing both growth factor expression and cell proliferation. Further studies are needed to understand the molecular and cellular mechanisms of how PARP regulates angiogenesis in different contexts. In addition, the process of wound healing is complicated and involves multiple cell types, including endothelial cells, epithelial cells and fibroblasts, monocytes, and bone marrow progenitor cells, as well as multiple cell behaviors, such as cell proliferation, migration, and adhesion. Cell-specific and genetic modification of PARP in animals will help us to better understand the role and mechanisms of PARP in the pathologic impairment of wound healing. Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesisJournal of Vascular SurgeryVol. 65Issue 4PreviewChronic nonhealing wounds are a major health problem for patients in the United States and worldwide. Diabetes and ischemia are two major risk factors behind impaired healing of chronic lower extremity wounds. Poly-ADP-ribose polymerase (PARP) is found to be overactivated with both ischemic and diabetic conditions. This study seeks a better understanding of the role of PARP in ischemic and diabetic wound healing, with a specific focus on angiogenesis and vasculogenesis. Full-Text PDF Open Archive