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MicroRNA-27a/b regulates cellular cholesterol efflux, influx and esterification/hydrolysis in THP-1 macrophages.

Abstract：

RATIONALE:Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis. OBJECTIVE:We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis. METHODS AND RESULTS:In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages. CONCLUSION:These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Zhang M,Wu JF,Chen WJ,Tang SL,Mo ZC,Tang YY,Li Y,Wang JL,Liu XY,Peng J,Chen K,He PP,Lv YC,Ouyang XP,Yao F,Tang DP,Cayabyab FS,Zhang DW,Zheng XL,Tian GP,Tang CK

doi

10.1016/j.atherosclerosis.2014.02.008

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

54-64

issue

1

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(14)00106-3

journal_volume

234

pub_type

杂志文章

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