Tiyerili, Vedat, Camara, Bakary, Becher, Marc U., Schrickel, Jan W., Luetjohann, Dieter, Mollenhauer, Martin, Baldus, Stephan, Nickenig, Georg and Andrie, Rene P. (2016). Neutrophil-derived myeloperoxidase promotes atherogenesis and neointima formation in mice. Int. J. Cardiol., 204. S. 29 - 37. CLARE: ELSEVIER IRELAND LTD. ISSN 1874-1754

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Abstract

Background: Myeloperoxidase (MPO), expressed mainly in neutrophils, is an enzyme linked to inflammation and oxidative stress. MPO is an independent prognostic marker in healthy individuals as well as in patients with coronary artery disease. In this present study we analyze the role of MPO in experimental atherogenesis and neointima formation after vascular injury in mice. Methods and results: 6-8 weeks old apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-cholesterol diet for 8 weeks with concomitant treatment with two different doses (10 mu g/mg bw vs. 20 mu g/mg bw) of 4-ABAH (MPO inhibitor). Application at lower dosage did not affect oxidative stress, endothelial function and atherosclerotic plaque development. 4-ABAH in higher dosage decreased inflammatory markers and vascular oxidative stress, consecutively improved endothelial function and reduced significantly atherosclerotic plaque development. To assess the role of circulating intracellular MPO, irradiated ApoE(-/-) mice were repopulated with bone marrow-derived cells from MPO(-/-)mice and were fed a high-cholesterol diet for 8 weeks. This MPO deficiency resulted in alleviated inflammation, reduced oxidative stress and improved endothelial function with a significant impact on plaque formation. To understand the possible role of MPO in vascular remodeling, we tested its effects on neointima formation following vascular injury in mice. MPO inhibition by 4-ABAH reduced significantly neointima formation. It was significantly reduced in MPO deficient mice, whereas transfer of spleen-derived neutrophils from WT mice enhanced it. Conclusion: Our data suggests a central role of MPO in the pathogenesis of atherogenesis and prefers pharmacological MPO inhibition as a therapeutic strategy for prevention and therapy of atherosclerosis and restenosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tiyerili, VedatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Camara, BakaryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becher, Marc U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schrickel, Jan W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luetjohann, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mollenhauer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldus, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nickenig, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrie, Rene P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-286322
DOI: 10.1016/j.ijcard.2015.11.128
Journal or Publication Title: Int. J. Cardiol.
Volume: 204
Page Range: S. 29 - 37
Date: 2016
Publisher: ELSEVIER IRELAND LTD
Place of Publication: CLARE
ISSN: 1874-1754
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HUMAN ATHEROSCLEROTIC LESIONS; HYPOCHLORITE-MODIFIED PROTEINS; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; LIPID-PEROXIDATION; RISK; MECHANISMS; EXPRESSION; OXIDATION; CATALYSTMultiple languages
Cardiac & Cardiovascular SystemsMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28632

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