title: Chronic and non-healing wounds: The story of vascular endothelial growth factor.
abstract: The pathophysiology of the chronicity and non-healing status of wounds remains unknown. This paper presents the following hypothesis: abnormal patterns of vascular endothelial growth factor receptors (VEGFRs) are the culprits of wound chronicity and non-healing. More specifically, for patients with poor circulation, the decreased VEGFR-2 level is the cause of poor wound healing; for patients with non-compromised circulation, for example, patients with concurrent chronic wounds and active autoimmune diseases, the increased VEGFR-1 level is related to the non-healing status of wounds. The hypothesis is supported by the following facts. VEGFR-1 is the main contributor for inflammation and VEGFR-2 facilitates angiogenesis; soluble VEGFR-1 (sVEGFR-1) inactivates both VEGFR-1 and VEGFR-2. Patients with auto-immune disease have abnormally increased VEGFR-1 and decreased sVEGFR. Wounds in patients with active autoimmune diseases have poor response to electric stimulation which facilitates chronic wound healing in patients without active autoimmune diseases via increasing vascular endothelial growth factor (VEGF) secretion. Patients with chronic wounds (including diabetic foot ulcers and venous leg ulcers) but no active autoimmune diseases have decreased VEGFR-2 levels. We thus believe that abnormal patterns of VEGFRs are the culprits of wound chronicity and non-healing. For wounds with compromised circulation, VEGFR-2 decrease contributes to its chronicity; whereas for wounds with non-compromised circulation, VEGFR-1 increase is the leading cause of the non-healing status of chronic wounds. Treatments and research in wound care should be tailored to target these changes based on circulation status of wounds. Complete elucidation of changes of VEGFRs in chronic and non-healing wounds will enhance our understandings in tissue healing and thus better our selection of appropriate treatments for chronic and non-healing wounds.
authors.affiliation: Department of Health Care Studies, Daemen College, Amherst, NY 14226, USA; Daemen College Physical Therapy Wound Care Clinic, Daemen College, Amherst, NY 14226, USA. Electronic address: kzhou@daemen.edu.
authors.forename: Kehua
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Internal Medicine and Sleep Center, Eye Hospital, China Academy of Chinese Medical Science, Beijing, China. Electronic address: dr.yan.ma@gmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Physical Therapy, Daemen College, Amherst, NY 14226, USA. Electronic address: mbrogan@daemen.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Brogan
mesh_terms: D001327:Autoimmune Diseases / Q000503:physiopathology; D002908:Chronic Disease; D017719:Diabetic Foot / Q000503:physiopathology; D004599:Electric Stimulation Therapy; D006801:Humans; D007249:Inflammation; D008962:Models, Theoretical; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology; D014945:Wound Healing; D014947:Wounds and Injuries / Q000503:physiopathology*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; C000588866:KDR protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2