HDL, cholesterol efflux, and ABCA1: Free from good and evil dualism
Homozygotes for loss-of-function mutations in ABCA1 cause Tangier disease. The phenotype of their markedly reduced or loss of blood high-density lipoprotein (HDL) cholesterol, as well as examination of ATP-binding cassette transporter A1 (ABCA1)-deficient mice, proved that ABCA1 is a key player in H...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Journal of Pharmacological Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861322000548 |
| _version_ | 1818000720683597824 |
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| author | Masatsune Ogura |
| author_facet | Masatsune Ogura |
| author_sort | Masatsune Ogura |
| collection | DOAJ |
| description | Homozygotes for loss-of-function mutations in ABCA1 cause Tangier disease. The phenotype of their markedly reduced or loss of blood high-density lipoprotein (HDL) cholesterol, as well as examination of ATP-binding cassette transporter A1 (ABCA1)-deficient mice, proved that ABCA1 is a key player in HDL production. The ABCA1-mediated cholesterol efflux is the first step in the reverse cholesterol transport system and understanding the regulation of its expression was expected to lead to the development of anti-atherosclerotic drugs. However, from the viewpoint of intracellular cholesterol homeostasis, it is difficult to say that simple activation of ABCA1 or promotion of cholesterol efflux is a good strategy. To date, there is no evidence that HDL-increasing drugs by enhancing ABCA1 expression prevent atherosclerotic disease in humans. On the other hand, in situations where intracellular cholesterol homeostasis is disrupted by inflammation, aging, or metabolic abnormalities, a strategy that restores reduced ABCA1 expression and cholesterol efflux in a timely and localized manner may be useful. |
| first_indexed | 2024-04-14T03:25:18Z |
| format | Article |
| id | doaj.art-78ac949d62c541238685335b80cd8884 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-14T03:25:18Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-78ac949d62c541238685335b80cd88842022-12-22T02:15:11ZengElsevierJournal of Pharmacological Sciences1347-86132022-10-0115028189HDL, cholesterol efflux, and ABCA1: Free from good and evil dualismMasatsune Ogura0Department of General Medical Science, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chiba 2608677, Japan; Department of Metabolism and Endocrinology, Eastern Chiba Medical Center, 3-6-2, Okayamadai, Togane 283-8686, Japan; Department of General Medical Science, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chiba 2608677, Japan.Homozygotes for loss-of-function mutations in ABCA1 cause Tangier disease. The phenotype of their markedly reduced or loss of blood high-density lipoprotein (HDL) cholesterol, as well as examination of ATP-binding cassette transporter A1 (ABCA1)-deficient mice, proved that ABCA1 is a key player in HDL production. The ABCA1-mediated cholesterol efflux is the first step in the reverse cholesterol transport system and understanding the regulation of its expression was expected to lead to the development of anti-atherosclerotic drugs. However, from the viewpoint of intracellular cholesterol homeostasis, it is difficult to say that simple activation of ABCA1 or promotion of cholesterol efflux is a good strategy. To date, there is no evidence that HDL-increasing drugs by enhancing ABCA1 expression prevent atherosclerotic disease in humans. On the other hand, in situations where intracellular cholesterol homeostasis is disrupted by inflammation, aging, or metabolic abnormalities, a strategy that restores reduced ABCA1 expression and cholesterol efflux in a timely and localized manner may be useful.http://www.sciencedirect.com/science/article/pii/S1347861322000548Intracellular cholesterol homeostasisHDLCholesterol effluxABCA1Drug discovery |
| spellingShingle | Masatsune Ogura HDL, cholesterol efflux, and ABCA1: Free from good and evil dualism Journal of Pharmacological Sciences Intracellular cholesterol homeostasis HDL Cholesterol efflux ABCA1 Drug discovery |
| title | HDL, cholesterol efflux, and ABCA1: Free from good and evil dualism |
| title_full | HDL, cholesterol efflux, and ABCA1: Free from good and evil dualism |
| title_fullStr | HDL, cholesterol efflux, and ABCA1: Free from good and evil dualism |
| title_full_unstemmed | HDL, cholesterol efflux, and ABCA1: Free from good and evil dualism |
| title_short | HDL, cholesterol efflux, and ABCA1: Free from good and evil dualism |
| title_sort | hdl cholesterol efflux and abca1 free from good and evil dualism |
| topic | Intracellular cholesterol homeostasis HDL Cholesterol efflux ABCA1 Drug discovery |
| url | http://www.sciencedirect.com/science/article/pii/S1347861322000548 |
| work_keys_str_mv | AT masatsuneogura hdlcholesteroleffluxandabca1freefromgoodandevildualism |