title: Combination of adrenomedullin with its binding protein accelerates cutaneous wound healing.
abstract: Cutaneous wound continues to cause significant morbidity and mortality in the setting of diseases such as diabetes and cardiovascular diseases. Despite advances in wound care management, there is still an unmet medical need exists for efficient therapy for cutaneous wound. Combined treatment of adrenomedullin (AM) and its binding protein-1 (AMBP-1) is protective in various disease conditions. To examine the effect of the combination treatment of AM and AMBP-1 on cutaneous wound healing, full-thickness 2.0-cm diameter circular excision wounds were surgically created on the dorsum of rats, saline (vehicle) or AM/AMBP-1 (96/320 μg kg BW) was topically applied to the wound daily and wound size measured. At days 3, 7, and 14, skin samples were collected from the wound sites. AM/AMBP-1 treated group had significantly smaller wound surface area than the vehicle group over the 14-day time course. At day 3, AM/AMBP-1 promoted neutrophil infiltration (MPO), increased cytokine levels (IL-6 and TNF-α), angiogenesis (CD31, VEGF and TGFβ-1) and cell proliferation (Ki67). By day 7 and 14, AM/AMBP-1 treatment decreased MPO, followed by a rapid resolution of inflammation characterized by a decrease in cytokines. At the matured stage, AM/AMBP-1 treatment increased the alpha smooth muscle actin expression (mature blood vessels) and Masson-Trichrome staining (collagen deposition) along the granulation area, and increased MMP-9 and decreased MMP-2 mRNA expressions. TGFβ-1 mRNA levels in AM/AMBP-1 group were 5.3 times lower than those in the vehicle group. AM/AMBP-1 accelerated wound healing by promoting angiogenesis, collagen deposition and remodeling. Treatment also shortened the days to reach plateau for wound closure. Thus, AM/AMBP-1 may be further developed as a therapeutic for cutaneous wound healing.
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Idrovo
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America; Center for Translational Research, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Weng-Lang
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America; Center for Translational Research, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Asha
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ajakaiye
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.
authors.forename: Cletus
authors.initials: C
authors.lastname: Cheyuo
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Prince
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Nicastro
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America.
authors.forename: Gene F
authors.initials: GF
authors.lastname: Coppa
authors.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, United States of America; Center for Translational Research, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D017242:Complement Factor H / Q000494:pharmacology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C481978:adrenomedullin-binding protein 1, rat; D053607:Adrenomedullin; D017242:Complement Factor H