| dc.description.abstract | A significant hallmark of the chronic inflammatory disease, atherosclerosis, is the accumulation of pro-inflammatory M1-like Macrophages (Macs) in coronary arteries that respond to pro-atherogenic stimuli (such as free fatty acids (FFAs) and oxidized LDLs (oxLDLs) and fail to digest lipids that contribute to the formation of foam cells in atherosclerotic plaques. Mechanisms that reduce Mac/ dendritic cells (DCs) inflammation, increase lipid degradation, and prevent foam cell formation are likely to decrease atherosclerosis progression.
The cell recycling program autophagy is critical to prevent lipotoxicity and reduce foam cell formation in atherosclerotic Macs and DCs. Increased autophagy helps regulate lipid metabolism and prevent the development of atherosclerosis. Mechanisms that regulate autophagy in Macs will likely reveal targets for the prevention of atherosclerosis.
Disrupted microbiota is linked with multiple diseases, including cardiovascular disease (CVD), and microbiota-derived TMAO metabolite production is one deleterious mechanism that promotes atherosclerosis. However, further research is necessary to identify new microbiota metabolites and determine their positive or negative role in CVD. Our overall goal in this project was to discuss the role of microbiota in promoting health and disease by the production of specific beneficial and detrimental metabolites that impact the development of atherosclerosis by jointly regulating chronic endotoxemic and lipotoxic inflammation, metabolic disruption in innate immune cells.
We have investigated tryptophan-derived microbiota metabolites, as novel aryl hydrocarbon receptor (AhR) ligands with immunomodulatory properties for APCs. In particular, indole metabolite. Indole is abundant in the GI tract and can enter into the blood circulation. Our objective in this study was to study the molecular mechanisms whereby microbiota regulates autophagy in Macs and to determine the functional consequences of microbiota-induced autophagy on innate immunity in response to atherogenic stimuli. | |
