Nitroxyl anion (HNO) donors are currently being assessed for their therapeutic utility in several cardiovascular disorders including heart failure. Here, we examine their effect on factors that precede atherosclerosis including endothelial cell and monocyte activation, leucocyte adhesion to the endothelium and macrophage polarization. Similar to the NO donor glyceryl trinitrate (GTN), the HNO donors Angeli's salt (AS) and isopropylamine NONOate (IPA/NO) decreased leucocyte adhesion to activated human umbilical vein endothelial cells (HUVECs) and mouse isolated aorta. This reduction in adhesion was accompanied by a reduction in intercellular adhesion molecule-1 (ICAM-1) and the cytokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) which was inhibitor of nuclear factor κB (NFκB) α (IκBα)- and subsequently NFκB-dependent. Intriguingly, the effects of AS on leucocyte adhesion, like those on vasodilation, were found to not be susceptible to pharmacological tolerance, unlike those observed with GTN. As well, HNO reduces monocyte activation and promotes polarization of M2 macrophages. Taken together, our data demonstrate that HNO donors can reduce factors that are associated with and which precede atherosclerosis and may thus be useful therapeutically. Furthermore, since the effects of the HNO donors were not subject to tolerance, this confers an additional advantage over NO donors.
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Corin protein expression in human renal proximal convoluted tubules as shown by brown staining in immunohistochemistry. See pp. 1655-1664 for further details. Image kindly provided by Qingyu Wu.
Research Article|
August 08 2016
Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarization
Karen L. Andrews;
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
†Cardiovascular Disease Program and Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
Correspondence: Dr Karen Andrews (email [email protected])
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Amanda K. Sampson;
Amanda K. Sampson
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
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Jennifer C. Irvine;
Jennifer C. Irvine
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
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Waled A. Shihata;
Waled A. Shihata
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
†Cardiovascular Disease Program and Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Danielle L. Michell;
Danielle L. Michell
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
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Natalie G. Lumsden;
Natalie G. Lumsden
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
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Chloe Lim;
Chloe Lim
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
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Olivier Huet;
Olivier Huet
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
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Grant R. Drummond;
Grant R. Drummond
†Cardiovascular Disease Program and Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Barbara K. Kemp-Harper;
Barbara K. Kemp-Harper
1
†Cardiovascular Disease Program and Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Jaye P. F. Chin-Dusting
Jaye P. F. Chin-Dusting
1
*Vascular Pharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia
†Cardiovascular Disease Program and Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, Victoria 3800, Australia
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Publisher: Portland Press Ltd
Received:
September 22 2015
Revision Received:
May 04 2016
Accepted:
May 26 2016
Accepted Manuscript online:
May 26 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (18): 1629–1640.
Article history
Received:
September 22 2015
Revision Received:
May 04 2016
Accepted:
May 26 2016
Accepted Manuscript online:
May 26 2016
Citation
Karen L. Andrews, Amanda K. Sampson, Jennifer C. Irvine, Waled A. Shihata, Danielle L. Michell, Natalie G. Lumsden, Chloe Lim, Olivier Huet, Grant R. Drummond, Barbara K. Kemp-Harper, Jaye P. F. Chin-Dusting; Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarization. Clin Sci (Lond) 1 September 2016; 130 (18): 1629–1640. doi: https://doi.org/10.1042/CS20160097
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