IN VIVO ACUTE SYSTEMIC INFLAMMATION, INDEPENDENTLY ON THE ETIOLOGY, AFFECTS HDL CHOLESTEROL EFFLUX CAPACITY

One of the primary antiatherogenic properties of HDL is its role in promoting reverse cholesterol transport (RCT), a process whereby excess cholesterol is removed from peripheral tissues and transported to the liver for excretion. The capacity of serum HDL to promote efflux of cholesterol from cells (cholesterol efflux capacity, CEC) represents an index of HDL functionality and its evaluation serves to estimate the efficiency of the entire process in humans. It has been suggested that HDL functionality changes may contribute to cardiovascular disease (CVD) protection. Inflammation is a central feature during all stages of atherosclerotic plaque formation with cytokines and chemokines orchestrating the influx of immune cells in disease vessels. Indeed, several systemic inflammatory diseases have been associated with an increased cardiovascular risk. The objective of this study was to analyze whether acute systemic inflammatory disease (sepsis) may affects the capacity of HDL to promote cholesterol efflux (CEC) through the main pathways (aqueous diffusion, AD, the scavenger receptor-BI, SR-BI and the ATP binding cassette transporters A1, ABCA1 and G1, ABCG1). Methods: HDL from 24 patients with sepsis of various etiology and 25 control subjects were tested for their cholesterol efflux capacity (CEC) via the four main pathways by using in vitro cell-based assays. HDL were isolated by precipitating the apoB-containing lipoproteins with PEG. Results: Patient with sepsis displayed a significant increase in the inflammatory markers such the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), together with a reduction in plasma lipid levels. HDL subclass distribution analysis showed a reduction in medium sized HDL and a trend toward an increase in large HDL in patients with sepsis; the small pre-beta HDL were unchanged in sepsis patients compared to control subjects. Aqueous diffusion (AD)-, SR-BI-, ABCG1-mediated CEC were markedly reduced in all patients with sepsis compared to control subjects (percent reduction in efflux were -28.6%, -46.9% and -24.8%, respectively; p<0.001). ABCA1-mediated CEC remained unchanged between patients and controls (mean percentage efflux ± SEM were 2.82±0.28% compared to 2.84±0.329%). Conclusion: subjects with acute systemic inflammation, irrespectively of the etiology of the syndrome, showed impairment of HDL AD-, SR-BI- and ABCG1-mediated CEC; such impairment appear to be the result of structural HDL changes and contribute to explain the accelerated atherosclerosis in these patients.