Aldosterone induces trained immunity: the role of fatty acid synthesis.
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ABSTRACT:
PROVIDER: PRJNA498108 | ENA |
REPOSITORIES: ENA
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Project description:Supranormal levels of aldosterone are associated with increased cardiovascular risk in humans, and with accelerated atherosclerosis in animal models. Atherosclerosis is a low-grade inflammatory disorder, with monocyte-derived macrophages as major drivers of plaque formation. Monocytes can adopt a long-term pro-inflammatory phenotype after brief stimulation with microbial pathogens or endogenous atherogenic lipoproteins via a process termed trained immunity. Using a primary human in vitro model, we demonstrate that aldosterone induces trained immunity via the mineralocorticoid receptor. We identify fatty acid synthesis as a crucial pathway necessary for the induction of trained immunity in monocyte-derived macrophages and demonstrate that pharmacological inhibition of this pathway blunts aldosterone-induced trained immunity. At the level of gene regulation, aldosterone promotes enrichment of the transcriptionally-permissive H3K4me3 modification at promoters of genes central to the fatty acid synthesis pathway. These data provide mechanistic insight into the contribution of aldosterone to inflammation, atherosclerosis and cardiovascular disease.
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