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Inhibition of myeloperoxidase increases revascularization and improves blood flow in a diabetic mouse model of hindlimb ischaemia
OBJECTIVE: Diabetes mellitus is a significant risk factor for peripheral artery disease. Diabetes mellitus induces chronic states of oxidative stress and vascular inflammation that increase neutrophil activation and release of myeloperoxidase. The goal of this study is to determine whether inhibitin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510377/ https://www.ncbi.nlm.nih.gov/pubmed/32223319 http://dx.doi.org/10.1177/1479164120907971 |
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author | Weihrauch, Dorothee Martin, Dustin P Jones, Deron Krolikowski, John Struve, Janine Naylor, Stephen Pritchard, Kirkwood A |
author_facet | Weihrauch, Dorothee Martin, Dustin P Jones, Deron Krolikowski, John Struve, Janine Naylor, Stephen Pritchard, Kirkwood A |
author_sort | Weihrauch, Dorothee |
collection | PubMed |
description | OBJECTIVE: Diabetes mellitus is a significant risk factor for peripheral artery disease. Diabetes mellitus induces chronic states of oxidative stress and vascular inflammation that increase neutrophil activation and release of myeloperoxidase. The goal of this study is to determine whether inhibiting myeloperoxidase reduces oxidative stress and neutrophil infiltration, increases vascularization, and improves blood flow in a diabetic murine model of hindlimb ischaemia. METHODS: Leptin receptor–deficient (db/db) mice were subjected to hindlimb ischaemia. Ischaemic mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC) to inhibit myeloperoxidase. After ligating the femoral artery, effects of treatments were determined with respect to hindlimb blood flow, neutrophil infiltration, oxidative damage, and the capability of hindlimb extracellular matrix to support human endothelial cell proliferation and migration. RESULTS: KYC treatment improved hindlimb blood flow at 7 and 14 days in db/db mice; decreased the formation of advanced glycation end products, 4-hydroxynonenal, and 3-chlorotyrosine; reduced neutrophil infiltration into the hindlimbs; and improved the ability of hindlimb extracellular matrix from db/db mice to support endothelial cell proliferation and migration. CONCLUSION: These results demonstrate that inhibiting myeloperoxidase reduces oxidative stress in ischaemic hindlimbs of db/db mice, which improves blood flow and reduces neutrophil infiltration such that hindlimb extracellular matrix from db/db mice supports endothelial cell proliferation and migration. |
format | Online Article Text |
id | pubmed-7510377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-75103772021-03-02 Inhibition of myeloperoxidase increases revascularization and improves blood flow in a diabetic mouse model of hindlimb ischaemia Weihrauch, Dorothee Martin, Dustin P Jones, Deron Krolikowski, John Struve, Janine Naylor, Stephen Pritchard, Kirkwood A Diab Vasc Dis Res Brief Report OBJECTIVE: Diabetes mellitus is a significant risk factor for peripheral artery disease. Diabetes mellitus induces chronic states of oxidative stress and vascular inflammation that increase neutrophil activation and release of myeloperoxidase. The goal of this study is to determine whether inhibiting myeloperoxidase reduces oxidative stress and neutrophil infiltration, increases vascularization, and improves blood flow in a diabetic murine model of hindlimb ischaemia. METHODS: Leptin receptor–deficient (db/db) mice were subjected to hindlimb ischaemia. Ischaemic mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC) to inhibit myeloperoxidase. After ligating the femoral artery, effects of treatments were determined with respect to hindlimb blood flow, neutrophil infiltration, oxidative damage, and the capability of hindlimb extracellular matrix to support human endothelial cell proliferation and migration. RESULTS: KYC treatment improved hindlimb blood flow at 7 and 14 days in db/db mice; decreased the formation of advanced glycation end products, 4-hydroxynonenal, and 3-chlorotyrosine; reduced neutrophil infiltration into the hindlimbs; and improved the ability of hindlimb extracellular matrix from db/db mice to support endothelial cell proliferation and migration. CONCLUSION: These results demonstrate that inhibiting myeloperoxidase reduces oxidative stress in ischaemic hindlimbs of db/db mice, which improves blood flow and reduces neutrophil infiltration such that hindlimb extracellular matrix from db/db mice supports endothelial cell proliferation and migration. SAGE Publications 2020-03-30 /pmc/articles/PMC7510377/ /pubmed/32223319 http://dx.doi.org/10.1177/1479164120907971 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Brief Report Weihrauch, Dorothee Martin, Dustin P Jones, Deron Krolikowski, John Struve, Janine Naylor, Stephen Pritchard, Kirkwood A Inhibition of myeloperoxidase increases revascularization and improves blood flow in a diabetic mouse model of hindlimb ischaemia |
title | Inhibition of myeloperoxidase increases revascularization and
improves blood flow in a diabetic mouse model of hindlimb
ischaemia |
title_full | Inhibition of myeloperoxidase increases revascularization and
improves blood flow in a diabetic mouse model of hindlimb
ischaemia |
title_fullStr | Inhibition of myeloperoxidase increases revascularization and
improves blood flow in a diabetic mouse model of hindlimb
ischaemia |
title_full_unstemmed | Inhibition of myeloperoxidase increases revascularization and
improves blood flow in a diabetic mouse model of hindlimb
ischaemia |
title_short | Inhibition of myeloperoxidase increases revascularization and
improves blood flow in a diabetic mouse model of hindlimb
ischaemia |
title_sort | inhibition of myeloperoxidase increases revascularization and
improves blood flow in a diabetic mouse model of hindlimb
ischaemia |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510377/ https://www.ncbi.nlm.nih.gov/pubmed/32223319 http://dx.doi.org/10.1177/1479164120907971 |
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