PMID- 34733931 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220428 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 9 IP - 17 DP - 2021 Sep TI - Artesunate attenuates foam cell formation by enhancing cholesterol efflux. PG - 1379 LID - 10.21037/atm-21-3551 [doi] LID - 1379 AB - BACKGROUND: Atherosclerosis is the main cause of many cardiovascular diseases and the second leading cause of death in elderly people. The formation of intimal macrophage-derived foam cells is a major feature of early atherosclerotic lesions. Little is known about the effects of artesunate (ART) on macrophage-derived foam cell formation. METHODS: Oil red O staining was employed to detect foam cell formation; colorimetric analysis was employed for cholesterol measurement; quantitative real time polymerase chain reaction (qRT-PCR) and western blot analysis were employed to assess messenger RNA (mRNA) and protein expression, respectively; enzyme-linked immunosorbent assay (ELISA) analyses were used to observe interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) release; and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to examine cell viability. RESULTS: It was revealed that ART attenuated oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation from THP-1-derived macrophages by decreasing cholesterol accumulation, and the effect might have occurred via enhanced cholesterol efflux. Additionally, ART decreased toll-like receptor 4 (TLR4) expression, increased adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) expression, and reduced the secretion of IL-6 and TNF-alpha. CONCLUSIONS: This study showed that ART attenuated the ox-LDL-induced formation of foam cells from THP-1-derived macrophages by increasing ABCA1 and ABCG1 expression via inhibiting TLR4 expression and reducing TNF-alpha and IL-6 secretion from macrophages induced by ox-LDL, which ultimately decreased the accumulation of cholesterol. It is worthwhile further investigate ART as a potential drug for the treatment of atherosclerosis. CI - 2021 Annals of Translational Medicine. All rights reserved. FAU - Qian, Yan AU - Qian Y AD - Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. FAU - Xia, Li AU - Xia L AD - Department of Liver Disease, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China. FAU - Wei, Lai AU - Wei L AD - Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. FAU - Jiang, Weiwei AU - Jiang W AD - Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC8506543 OTO - NOTNLM OT - Artesunate (ART) OT - atherosclerosis OT - cholesterol efflux OT - foam cell COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-3551). The authors have no conflicts of interest to declare. EDAT- 2021/11/05 06:00 MHDA- 2021/11/05 06:01 PMCR- 2021/09/01 CRDT- 2021/11/04 06:28 PHST- 2021/06/07 00:00 [received] PHST- 2021/08/11 00:00 [accepted] PHST- 2021/11/04 06:28 [entrez] PHST- 2021/11/05 06:00 [pubmed] PHST- 2021/11/05 06:01 [medline] PHST- 2021/09/01 00:00 [pmc-release] AID - atm-09-17-1379 [pii] AID - 10.21037/atm-21-3551 [doi] PST - ppublish SO - Ann Transl Med. 2021 Sep;9(17):1379. doi: 10.21037/atm-21-3551.