Lactobacillus acidophilus K301 Inhibits Atherogenesis via Induction of 24 (S), 25-Epoxycholesterol-Mediated ABCA1 and ABCG1 Production and Cholesterol Efflux in Macrophages.
Lactobacillus acidophilus species are well-known probiotics with the beneficial activity of regulating cholesterol levels. In this study, we showed that L. acidophilus K301 reduced the level of cholesterol through reverse transport in macrophages. L. acidophilus K301 upregulated the mRNA and protein levels of genes such as ATP-binding cassette A1 (ABCA1) and ATP-binding cassette G1 (ABCG1) under the control of liver X receptor (LXR), resulting in increased apoA-I-dependent cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. L. acidophilus K301 induced both ABCA1 and ABCG1 through the endogenous LXR agonist 24(S), 25-epoxcycholesterol, which is synthesized by intracellular cholesterol synthetic pathways. In vivo studies using L. acidophilus K301-treated ApoE-/- mice showed reduced accumulation of lipoproteins in the arterial lumen. The inhibitory effects of L. acidophilus K301 on accumulation of lipoprotein in atherosclerotic plaques were mediated by the induction of squalene reductase (SQLE) and oxidosqualene cyclase (OSC) and resulted in ABCA1-mediated cholesterol efflux. Taken together, our findings revealed that Lactobacillus acidophilus K301 regulates the expression of genes related to cholesterol reverse transport via the induction of endogenous LXR agonist, suggesting the therapeutic potential of Lactobacillus acidophilus K301 as an anti-atherosclerotic agent.
Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin, 446-701, Republic of Korea.|Skin Biotechnology Center, Kyung Hee University, Yongin, 446-701, Republic of Korea.
Yi-Fan
YF
Hong
Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin, 446-701, Republic of Korea.|Skin Biotechnology Center, Kyung Hee University, Yongin, 446-701, Republic of Korea.
Hangeun
H
Kim
Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin, 446-701, Republic of Korea.
Hye Sun
HS
Kim
Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin, 446-701, Republic of Korea.
Woo Jung
WJ
Park
Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin, 446-701, Republic of Korea.
Joo-Yun
JY
Kim
Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin, 446-701, Republic of Korea.|Skin Biotechnology Center, Kyung Hee University, Yongin, 446-701, Republic of Korea.|RNA Inc., #308 Life Sceince Building, Kyung Hee University Global Campus, Yongin, 446-701, Republic of Korea.
Dae Kyun
DK
Chung
D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism; D007779:Lactobacillus acidophilus / Q000502:physiology*; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019936:Probiotics / Q000494:pharmacology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D002784:Cholesterol; D013186:Farnesyl-Diphosphate Farnesyltransferase; D019751:Intramolecular Transferases; D000071518:Liver X Receptors; D013755:Tetradecanoylphorbol Acetate; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse; C028358:24,25-epoxycholesterol; C021924:lanosterol synthase