Abstract 085: Monocytes-derived Cytokines Induce Endothelial Dysfunction In Primary Aldosteronism

Abstract

Due to aldosterone excess and its pleotropic effects, patients with primary aldosteronism (PA) are exposed to high rates of cardiovascular events. Endothelial dysfunction is the first step in the development of vascular disease and monocytes are an important immune cell type inducing vascular damage. Therefore, we measured endothelial function between PA patients and healthy controls and analyzed the impact of monocytes-derived cyctokines on the development of endothelial dysfunction. Endothelial function was measured in 13 healthy controls, 42 PA patients before and in 22 patients 6 months after initiation of a specific treatment using flow mediated dilation method (FMD). Monocytes were isolated from 6 healthy individuals as well as from 8 PA patients before and treatment. Cytokine profile was measured by a Human Cytokine 17-plex Assay (Bio-rad). The effects of monocyte-derived cytokines on endothelial function were studied by wire myography in pre-constricted thoracic aortic pieces of healthy mice. FMD was significantly lower among PA patients compared to controls. Surgical or pharmacological treatment significantly improved endothelial function in PA patients. Monocytes from untreated patients with PA secreted significantly higher concentrations of the following cytokines and growth factors than healthy controls: G-CSF, IFN-γ, TNF-α, IL-6, IL-10, IL-8, IL-17, and MCP-1. Especially concentrations of IL-6 (388 (351-580)pg/ml vs. 36(4-268)pg/ml, p<0.05) and TNF-α (95(48-135)pg/ml vs 17(5-41)pg/ml, p<0.05) were much higher among PA patients. In pre-constricted murine aortas, 24 hours incubation of the secretome from untreated patients with PA induced an impaired endothelial vasodilation compared to the secretome of the controls. Interestingly, in comparison to untreated patients, treatment of PA not only reduced monocytes-derived cytokine levels, but also improved endothelial dysfunction in pre-constricted aortas incubated with the corresponding secretome. Endothelial function is impaired in PA. This impairment seem to be in part mediated by an increased release of pro-inflammatory cytokines from monocytes. PA treatment reduced the pro-inflammatory activity of monocytes and improved endothelial function.