title: CARP, a cardiac ankyrin repeat protein, is up-regulated during wound healing and induces angiogenesis in experimental granulation tissue.
abstract: Cardiac ankyrin repeat protein (CARP) was identified by subtractive hybridization as one of a group of genes that are rapidly modulated by acute wounding of mouse skin. Quantitative RT-PCR showed that CARP was strongly induced during the first day after wounding (157.1-fold), and the high level persisted for up to 14 days. Immunohistochemistry and in situ hybridization revealed that CARP was expressed in skeletal muscle, vessel wall, hair follicle, inflammatory cells, and epidermis in the wound area. To examine the effects of CARP on wound healing, we developed an adenoviral CARP vector to treat subcutaneously implanted sponges in either rats or Flk-1(LacZ) knock-in mice. Four days after infection, CARP-infected sponges in rats showed a remarkable increase in the vascular component in granulation tissue as compared to Ad-LacZ controls. This result was confirmed by CD34 immunostaining. By 7 days post-infection of sponge implants in Flk-1(LacZ) knock-in mice, granulation tissue showed many more LacZ-positive cells in Ad-CARP-infected sponges than in virus controls. Ad-CARP treatment also induced neovascularization and increased blood perfusion in rabbit excisional wounds in and ischemic rat wounds. These findings indicate that CARP could play a unique role in therapeutic angiogenesis during wound healing.
authors.affiliation: Department of Pathology C3321 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232-2562, USA.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Shi
authors.forename: Birgit
authors.initials: B
authors.lastname: Reitmaier
authors.forename: Johannes
authors.initials: J
authors.lastname: Regenbogen
authors.forename: R Michael
authors.initials: RM
authors.lastname: Slowey
authors.forename: Susan R
authors.initials: SR
authors.lastname: Opalenik
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Andreas
authors.initials: A
authors.lastname: Goppelt
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Davidson
mesh_terms: D042501:Angiogenic Proteins / Q000502:physiology; D000818:Animals; D017089:Ankyrin Repeat / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009124:Muscle Proteins; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000235:genetics*; D014947:Wounds and Injuries / Q000235:genetics / Q000473:pathology
chemical_list: D042501:Angiogenic Proteins; C104844:Ankrd1 protein, mouse; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins