Arsenic on cholesterol efflux and the expression of ABCA1, ABCG1 and SRBI / 预防医学

ABSTRACT

Objective@#To explore the impact of arsenic on cholesterol efflux and the expression of ATP-binding cassette, sub-family A, member 1 ( ABCA1 ), ATP-binding cassette transporter G1 ( ABCG1 ), and scavenger receptor class B member I ( SRBI ) in macrophages, so as to provide the evidence for the mechanism of arsenic induced atherosclerosis.@*Methods@#The human myeloid leukemia mononuclear cells ( THP-1 ), induced by phorbol myristate acetate, and mouse primary macrophages were treated with 0, 0.625, 1.25, 2.5 and 5 μmol/L NaAsO2 for 48 hours. Then the cells treated with 2.5 μmol/L NaAsO2 were changed to arsenic free mediums for 48 hours and collected every 12 hours to analyze the time effect of arsenic. The expression levels of ABCA1, ABCG1 and SRBI were determined by quantitative polymerase chain reaction and western blotting. Cholesterol efflux rates were measured by 3H isotope tracer. @*Results@#Arsenic significantly down-regulated the expression levels of ABCA1 and ABCG1, and cholesterol efflux in a dose-dependent manner. The levels of ABCA1 mRNA decreased by 69% and 72%, the levels of ABCG1 mRNA decreased by 42% and 34%, and the rate of cholesterol efflux decreased by 55% and 59% in THP-1 and mouse primary macrophages cells treated with 5 μmol/L NaAsO2 ( all P<0.05 ). Arsenic had no significant effect on SRBI expression ( all P>0.05 ). Arsenic inhibited ABCA1 expression and cholesterol efflux in THP-1 in a time-dependent manner. Compared with cells before the exposure of arsenic, the level of ABCA1 mRNA and the rate of cholesterol efflux in THP-1 bottomed at 48 hours by 43% and 42%, and gradually recovered when arsenic was removed. @*Conclusions@#Arsenic inhibits cholesterol efflux by down-regulating the expression of ABCA1 and ABCG1 in macrophages.