Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarization

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

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10 Citations (Scopus)

Abstract

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) a (IκBa)- 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.

Original languageEnglish
Pages (from-to)1629-1640
Number of pages12
JournalClinical Science
Volume130
Issue number18
DOIs
Publication statusPublished - 2016

Keywords

  • Inflammation
  • Leucocyte adhesion
  • Nitrate tolerance
  • Nitric oxide
  • Nitroxyl

Cite this

Andrews, K. L., Sampson, A. K., Irvine, J. C., Shihata, W. A., Michell, D. L., Lumsden, N. G., Lim, C., Huet, O., Drummond, G. R., Kemp-Harper, B. K., & Chin-Dusting, J. P. F. (2016). Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarization. Clinical Science, 130(18), 1629-1640. https://doi.org/10.1042/CS20160097