Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing.
Vascular deficits are a fundamental contributing factor of diabetes-associated diseases. Although previous studies have demonstrated that the pro-angiogenic phase of wound healing is blunted in diabetes, a comprehensive understanding of the mechanisms that regulate skin revascularization and capilla...
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doaj-944f7afd701a4628bc48d45e9ddcaa442021-03-03T21:43:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01154e023196210.1371/journal.pone.0231962Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing.Uzoagu A OkonkwoLin ChenDa MaVeronica A HaywoodMay BarakatNorifumi UraoLuisa A DiPietroVascular deficits are a fundamental contributing factor of diabetes-associated diseases. Although previous studies have demonstrated that the pro-angiogenic phase of wound healing is blunted in diabetes, a comprehensive understanding of the mechanisms that regulate skin revascularization and capillary stabilization in diabetic wounds is lacking. Using a mouse model of diabetic wound healing, we performed microCT analysis of the 3-dimensional architecture of the capillary bed. As compared to wild type, vessel surface area, branch junction number, total vessel length, and total branch number were significantly decreased in wounds of diabetic mice as compared to WT mice. Diabetic mouse wounds also had significantly increased capillary permeability and decreased pericyte coverage of capillaries. Diabetic wounds exhibited significant perturbations in the expression of factors that affect vascular regrowth, maturation and stability. Specifically, the expression of VEGF-A, Sprouty2, PEDF, LRP6, Thrombospondin 1, CXCL10, CXCR3, PDGFR-β, HB-EGF, EGFR, TGF-β1, Semaphorin3a, Neuropilin 1, angiopoietin 2, NG2, and RGS5 were down-regulated in diabetic wounds. Together, these studies provide novel information about the complexity of the perturbation of angiogenesis in diabetic wounds. Targeting factors responsible for wound resolution and vascular pruning, as well those that affect pericyte recruitment, maturation, and stability may have the potential to improve diabetic skin wound healing.https://doi.org/10.1371/journal.pone.0231962 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Uzoagu A Okonkwo Lin Chen Da Ma Veronica A Haywood May Barakat Norifumi Urao Luisa A DiPietro |
spellingShingle |
Uzoagu A Okonkwo Lin Chen Da Ma Veronica A Haywood May Barakat Norifumi Urao Luisa A DiPietro Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing. PLoS ONE |
author_facet |
Uzoagu A Okonkwo Lin Chen Da Ma Veronica A Haywood May Barakat Norifumi Urao Luisa A DiPietro |
author_sort |
Uzoagu A Okonkwo |
title |
Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing. |
title_short |
Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing. |
title_full |
Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing. |
title_fullStr |
Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing. |
title_full_unstemmed |
Compromised angiogenesis and vascular Integrity in impaired diabetic wound healing. |
title_sort |
compromised angiogenesis and vascular integrity in impaired diabetic wound healing. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
Vascular deficits are a fundamental contributing factor of diabetes-associated diseases. Although previous studies have demonstrated that the pro-angiogenic phase of wound healing is blunted in diabetes, a comprehensive understanding of the mechanisms that regulate skin revascularization and capillary stabilization in diabetic wounds is lacking. Using a mouse model of diabetic wound healing, we performed microCT analysis of the 3-dimensional architecture of the capillary bed. As compared to wild type, vessel surface area, branch junction number, total vessel length, and total branch number were significantly decreased in wounds of diabetic mice as compared to WT mice. Diabetic mouse wounds also had significantly increased capillary permeability and decreased pericyte coverage of capillaries. Diabetic wounds exhibited significant perturbations in the expression of factors that affect vascular regrowth, maturation and stability. Specifically, the expression of VEGF-A, Sprouty2, PEDF, LRP6, Thrombospondin 1, CXCL10, CXCR3, PDGFR-β, HB-EGF, EGFR, TGF-β1, Semaphorin3a, Neuropilin 1, angiopoietin 2, NG2, and RGS5 were down-regulated in diabetic wounds. Together, these studies provide novel information about the complexity of the perturbation of angiogenesis in diabetic wounds. Targeting factors responsible for wound resolution and vascular pruning, as well those that affect pericyte recruitment, maturation, and stability may have the potential to improve diabetic skin wound healing. |
url |
https://doi.org/10.1371/journal.pone.0231962 |
work_keys_str_mv |
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