Inhibition of myeloperoxidase increases revascularization and improves blood flow in a diabetic mouse model of hindlimb ischaemia
| Autor: | John G. Krolikowski, Dustin P. Martin, Deron W. Jones, Kirkwood A. Pritchard, Stephen Naylor, Dorothee Weihrauch, Janine A. Struve |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Neutrophils Endocrinology Diabetes and Metabolism medicine.medical_treatment Hindlimb Disease 030204 cardiovascular system & hematology medicine.disease_cause Diabetes mellitus 0302 clinical medicine limb ischaemia Cell Movement Ischemia blood flow Enzyme Inhibitors Cells Cultured Mice Knockout 0303 health sciences biology Brief Report Extracellular Matrix myeloperoxidase Neutrophil Infiltration Myeloperoxidase Cardiology Receptors Leptin Cardiology and Cardiovascular Medicine Oligopeptides Signal Transduction medicine.medical_specialty animal structures Neovascularization Physiologic peripheral artery disease Revascularization 03 medical and health sciences Internal medicine Human Umbilical Vein Endothelial Cells Internal Medicine medicine Animals Humans Muscle Skeletal Cell Proliferation Peroxidase 030304 developmental biology business.industry Blood flow medicine.disease Mice Inbred C57BL Disease Models Animal Oxidative Stress Regional Blood Flow biology.protein Angiogenesis Inducing Agents business Oxidative stress |
| Zdroj: | Diabetes & Vascular Disease Research |
| ISSN: | 1752-8984 1479-1641 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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