The Effect Of Macrophage ABCG1 On HDL And Its Mechanism

Background and ObjectiveAtherosclerosis(AS)characterized by stenosis,is a serious threat to human health.Involved in the reverse transport of cholesterol,macrophage ABCG1 and HDL are closely related to AS.miRNAs are non-coding RNAs of 22-25 nucleotides in length that affect the development of AS.Our previous clinical studies suggest that ABCG1 has a complex effect on AS and may have AS-promoting effects.To investigate its possible mechanism,we constructed a THP-1 cell lines with ABCG1 knockdown or overexpression and studied its influence on HDL from the perspective of micRNA.MethodsTHP-1 cells were infected with the lentiviral vecto.The stable knockdown cell lines were selected by puromycin and then verified.High-throughput sequencing was used to screen the miRNA differential expression profile of macrophages with ABCG1 differential expression.Then macrophages with ABCG1 differential expression were co-cultured with HepG2 cells and the expression levels of apoA-1,SAA and LCAT in HepG2 cells were measured.Bioinformatics methods were used to predict the differential micRNA affecting apoA-1,SAA,and LCAT.ResultsThe expression of ABCG1 in THP-1 cell line with ABCG1 knockdown was decreased,and the expression of ABCG1 of overexpression cell line was increased.Through high-throughput sequencing,138 differentially expressed miRNAs were found.After the co-culture,the ABCG1 low-expression group APOA1 and LCAT were up-regulated and SAA1 was down-regulated in HepG2 cells,compared with the control group.Through bioinformatics analysis,five micRNAs,hsa-miR-942-5p,hsa-miR-223-5p,hsa-miR-301b-3p,hsa-miR-129-5p and hsa-miR-2682-5p were selected,which were associated with apoA-1,SAA,and LCAT.ConclusionTHP-1 cell line with ABCG1 knockdown or overexpression was successfully constructed.The miRNA differential expression profile of macrophages with ABCG1 differential expression was obtained.Low expression of macrophage ABCG1 has an effect on apoA-1,SAA,and LCAT.