Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol

TOLEDO, J. D.; GRASA, MARÍA DEL MAR; GONZALEZ MARINA CECILIA; ESTEVE, MONTSERRAT; GARDA, H. A.; LEDDA, ANGELO; JOSE GULFO

Córdoba

Congreso; 51 Congreso de la Sociedad argentina de Bioquímica y Biología Molecular (SAIB); 2016

SAIB

Data about glucocorticoidsrole in the development of atherosclerosis are controversial showing differenteffects in human than in experimental animal models. Atherosclerosis is theresult of a chronic inflammatory response to an injured endothelium where anuncontrolled uptake of OxLDL (oxidized low density lipoprotein) by macrophagestriggers the development of foam cells, the main component of fatty streaks inatherosclerotic plaque. There are few data about the direct effect ofglucocorticoids in macrophages of atherosclerotic plaque. The aim of the studywas to elucidate the role of glucocorticoids in the development of foam cellsin atherosclerosis initiation. For this purpose we used THP1 cellsdifferentiated to macrophages with phorbol esters and incubated with OxLDLalone or with cortisol or cortisone. Ours results showed that cortisol andcortisone decreased significantly the inflammation promoted by OxLDL, and alsodiminished the expression of genes involved in influx and efflux of cholesterolresulting in a reduced lipid accumulation. Our results indicate a direct effectof glucocorticoids on macrophages braking atherosclerosis initiation, reducingpro-inflammatory markers and OxLDL uptake and cholesterol re-esterification, butalso inhibiting cholesterol output. These effects appear to be mediated, at leastin part, by 11bHSD1 activity.