COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model.
Microvascular dysfunction is a major cause of impaired wound healing seen in diabetic patients. Therefore, reestablishment of structural and functional microvasculature could be beneficial to promote wound healing in these patients. Angiopoietin-1 (Ang1) is a specific growth factor functioning to generate a stable and functional vasculature through the Tie2 and Tie1 receptors. Here we determined the effectiveness of cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable, and potent form of Ang1, on promotion of healing in cutaneous wounds of diabetic mice. An excisional full-thickness wound was made in the dorsal side of the tail of diabetic (db/db) mice, and mice were then treated systemically with adenovirus (Ade) encoding COMP-Ang1 or with control virus encoding beta-gal (Ade-beta-gal) or treated topically with recombinant COMP-Ang1 protein or BSA. Time course observations revealed that mice treated with Ade-COMP-Ang1 or COMP-Ang1 protein showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis and lymphangiogenesis, and higher blood flow in the wound region compared with mice treated with control virus or BSA. COMP-Ang1 promotion of wound closure and angiogenesis was not dependent on endothelial nitric oxide synthase or inducible nitric oxide synthase alone. Taken together, these findings indicate that COMP-Ang1 can promote wound healing in diabetes through enhanced angiogenesis, lymphangiogenesis, and blood flow.
Cho
Chung-Hyun
CH
Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Guseong-dong, Daejeon 305-701, Korea.
Sung
Hoon-Ki
HK
Kim
Kyung-Tae
KT
Cheon
Hyae Gyeong
HG
Oh
Goo Taeg
GT
Hong
Hyo Jeong
HJ
Yoo
Ook-Joon
OJ
Koh
Gou Young
GY
D042683:Angiopoietin-1 / Q000235:genetics / Q000627:therapeutic use*; D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D004423:Ear / Q000098:blood supply / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000627:therapeutic use*; D006023:Glycoproteins / Q000235:genetics / Q000627:therapeutic use*; D042583:Lymphangiogenesis / Q000187:drug effects*; D064235:Matrilin Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects*; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D013623:Tail / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
D042683:Angiopoietin-1; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; D011994:Recombinant Proteins; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse