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

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, leukocyte adhesion to the endothelium and macrophage polarisation. Similar to the NO donor, glyceryl trinitrate, the HNO donors, Angeli's Salt and isopropylamine NONOate decreased leukocyte adhesion to activated human umbilical vein endothelial cells and mouse isolated aorta. This reduction in adhesion was accompanied by a reduction in the adhesion molecule ICAM-1 and the cytokines MCP-1 and IL-6 which was IBα and subsequently NFB dependent. Intriguingly, the effects of Angeli's salt on leukocyte adhesion, like those to vasodilation, were found to not be susceptible to pharmacological tolerance, unlike those observed to glyceryl trinitrate.  As well, HNO reduces monocyte activation and promotes polarisation 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.

Source: Clinical Science - May 25, 2016 Category: Biomedical Science Authors: Andrews, K. L., Sampson, A. K., Irvine, J. C., Shihata, W. A., Michell, D., Lumsden, N. G., Lim, C., Huet, O., Kemp-Harper, B., Chin-Dusting, J. P. Tags: PublishAheadOfPrint Source Type: research