Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol export from macrophages in vivo
Open accessAbstract
Eight proteins potentially involved in cholesterol efflux [ABCA1, ABCG1, CYP27A1, phospholipid transfer protein (PLTP), scavenger receptor type BI (SR-BI), caveolin-1, cholesteryl ester transfer protein, and apolipoprotein A-I (apoA-I)] were overexpressed alone or in combination in RAW 264.7 macrophages. When apoA-I was used as an acceptor, overexpression of the combination of ABCA1, CYP27A1, PLTP, and SR-BI (Combination I) enhanced the efflux by 4.3-fold. It was established that the stimulation of efflux was due to increased abundance of ABCA1 and increased apoA-I binding to non-ABCA1 sites on macrophages. This combination caused only a small increase of the efflux to isolated HDL. When HDL was used as an acceptor, overexpression of caveolin-1 or a combination of caveolin-1 and SR-BI (Combination II) was the most active, doubling the efflux to HDL, without affecting the efflux to apoA-I. When tested in the in vivo mouse model of cholesterol efflux, overexpression of ABCA1 and Combination I elevated cholesterol export from macrophages to plasma, liver, and feces, whereas overexpression of caveolin-1 or Combination II did not have an effect. We conclude that pathways of cholesterol efflux using apoA-I as an acceptor make a predominant contribution to cholesterol export from macrophages in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CAV1 has been proposed to participate in the regulation of cholesterol efflux to HDL, possibly in interaction with ABCG1.
“CAV1 has been proposed to participate in the regulation of cholesterol efflux to HDL6061, possibly in interaction with ABCG161.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [60]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
Wang, N., Lan, D., Chen, W., Matsuura, F., & Tall, A. R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403506101 · Cited by 1,059 · see citing works
Basu, S. K., Goldstein, J. L., Anderson, G. W., & Brown, M. S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.9.3178 · Cited by 1,021 · see citing works
Kennedy, M. A., Barrera, G. C., Nakamura, K., Baldán, Á., Tarr, P. T., Fishbein, M. C., Frank, J. S., Francone, O. L., & Edwards, P. A. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.01.002 · Cited by 885 · see citing works
Scavenger Receptor BI Promotes High Density Lipoprotein-mediated Cellular Cholesterol Efflux
Ji, Y. I., Jian, B., Wang, N., Sun, Y., Moya, M. D. L. L., Phillips, M. C., Rothblat, G. H., Swaney, J. B., & Tall, A. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.34.20982 · Cited by 694 · see citing works
Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo
Wang, X., Collins, H. L., Ranalletta, M., Fuki, I. V., Billheimer, J. T., Rothblat, G. H., Tall, A. R., & Rader, D. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32057 · Cited by 593 · see citing works
Razani, B., Combs, T. P., Wang, X., Frank, P. G., Park, D. S., Russell, R. G., Li, M., Tang, B., Jelicks, L. A., Scherer, P. E., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110970200 · Cited by 579 · see citing works
Wang, N., Silver, D. L., Costet, P., & Tall, A. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005438200 · Cited by 569 · see citing works
ABCA1 and ABCG1 Synergize to Mediate Cholesterol Export to ApoA-I
Gelissen, I. C., Harris, M., Rye, K., Quinn, C. M., Brown, A. J., Kockx, M., Cartland, S. P., Packianathan, M., Kritharides, L., & Jessup, W. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000200082.58536.e1 · Cited by 430 · see citing works
Increased Atherosclerosis in Hyperlipidemic Mice With Inactivation of ABCA1 in Macrophages
Aiello, R. J., Brees, D., Bourassa, P.-A., Royer, L., Lindsey, S., Coskran, T., Haghpassand, M., & Francone, O. L. (2002) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000014804.35824.da · Cited by 390 · see citing works
Vedhachalam, C., Duong, P. T., Nickel, M., Nguyen, D., Dhanasekaran, P., Saito, H., Rothblat, G. H., Lund‐Katz, S., & Phillips, M. C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704590200 · Cited by 337 · see citing works
The roles of different pathways in the release of cholesterol from macrophages
Adorni, M. P., Zimetti, F., Billheimer, J. T., Wang, N., Rader, D. J., Phillips, M. C., & Rothblat, G. H. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700274-jlr200 · Cited by 332 · see citing works
Joyce, C. W., Amar, M. J., Lambert, G. C., Vaisman, B. L., Paigen, B. J., Najib-Fruchart, J., Hoyt, R. F., Neufeld, E. D., Remaley, A. T., Fredrickson, D. S., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012587699 · Cited by 269 · see citing works
ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins
Oram, J. F., & Vaughan, A. M. (2000) · Current Opinion in Lipidology · doi:10.1097/00041433-200006000-00005 · Cited by 266 · see citing works
Increased ABCA1 activity protects against atherosclerosis
Singaraja, R. R., Fievet, C., Castro, G., James, E. R., Hennuyer, N., Clee, S. M., Bissada, N., Choy, J. C., Fruchart, J.-C., McManus, B. M., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15748 · Cited by 250 · see citing works
Increased ABCA1 activity protects against atherosclerosis
Singaraja, R. R., Fiévet, C., Castro, G. R., James, E. R., Hennuyer, N., Clee, S. M., Bissada, N., Choy, J. C., Fruchart, J., McManus, B. M., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215748 · Cited by 220 · see citing works
Out, R., Hoekstra, M., Hildebrand, R. B., Kruit, J. K., Meurs, I., Li, Z., Kuipers, F., van Berkel, T. J. C., & Eck, M. V. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000237629.29842.4c · Cited by 204 · see citing works
ABCA1 redistributes membrane cholesterol independent of apolipoprotein interactions
Vaughan, A. M., & Oram, J. F. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m300078-jlr200 · Cited by 203 · see citing works
Fielding, P. E., Nagao, K., Hakamata, H., Chimini, G., & Fielding, C. J. (2000) · Biochemistry · doi:10.1021/bi0004192 · Cited by 202 · see citing works
Oram, J. F., Wolfbauer, G., Vaughan, A. M., Tang, C., & Albers, J. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m310695200 · Cited by 148 · see citing works
Expression of Caveolin-1 Enhances Cholesterol Efflux in Hepatic Cells
Fu, Y., Hoang, A., Escher, G., Parton, R. G., Krozowski, Z. S., & Sviridov, D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311061200 · Cited by 115 · see citing works
Self-citationChen, W., Silver, D. L., Smith, J. D., & Tall, A. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004552200 · Cited by 113 · see citing works
Hassan, H. H., Denis, M., Lee, D.-Y. D., Iatan, I., Nyholt, D., Ruel, I. L., Krimbou, L., & Genest, J. J. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700206-jlr200 · Cited by 95 · see citing works
Human Sterol 27-Hydroxylase (CYP27) Overexpressor Transgenic Mouse Model
Meir, K. S., Kitsberg, D., Alkalay, I., Szafer, F., Rosen, H., Shpitzen, S., Avi, L. B., Staels, B., Fiévet, C., Meiner, V., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201122200 · Cited by 81 · see citing works
Expression of Sterol 27-Hydroxylase (CYP27A1) Enhances Cholesterol Efflux
Escher, G., Krozowski, Z. S., Croft, K. D., & Sviridov, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212780200 · Cited by 81 · see citing works
Self-citationTotal Body ABCG1 Expression Protects Against Early Atherosclerotic Lesion Development in Mice
Out, R., Hoekstra, M., Meurs, I., de Vos, P., Kuiper, J., Eck, M. V., & van Berkel, T. J. C. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000257136.24308.0c · Cited by 80 · see citing works
Tchoua, U., D’Souza, W., Mukhamedova, N., Blum, D., Niesor, E. J., Mizrahi, J. L., Maugeais, C., & Sviridov, D. (2007) · Cardiovascular Research · doi:10.1093/cvr/cvm087 · Cited by 72 · see citing works
Self-citationNagao, K., Takahashi, K., Hanada, K., Kioka, N., Matsuo, M., & Ueda, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611230200 · Cited by 65 · see citing works
Efflux of Cellular Cholesterol and Phospholipid to Apolipoprotein A-I Mutants
Sviridov, D., Pyle, L. E., & Fidge, N. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.52.33277 · Cited by 65 · see citing works
Self-citationZhang, Z., Yamashita, S., Hirano, K., Nakagawa-Toyama, Y., Matsuyama, A., Nishida, M., Sakai, N., Fukasawa, M., Arai, H., Miyagawa, J., et al. (2001) · Atherosclerosis · doi:10.1016/s0021-9150(01)00490-7 · Cited by 62 · see citing works
Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects
Catalano, G., Duchêne, E., Julia, Z., Goff, W. L., Bruckert, É., Chapman, M. J., & Guérin, M. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700510-jlr200 · Cited by 60 · see citing works
Wang, M., Kiss, R. S., Franklin, V., McBride, H. M., Whitman, S. C., & Marcel, Y. L. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600470-jlr200 · Cited by 57 · see citing works
Potential involvement of dissociated apoA-I in the ABCA1-dependent cellular lipid release by HDL
Okuhira, K., Tsujita, M., Yamauchi, Y., et al. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m300257-jlr200 · Cited by 56 · see citing works
SR-BI inhibits ABCG1-stimulated net cholesterol efflux from cells to plasma HDL
Yvan‐Charvet, L., Pagler, T. A., Wang, N., Senokuchi, T., Brundert, M., Li, H., Rinninger, F., & Tall, A. R. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700200-jlr200 · Cited by 54 · see citing works
Major, A. S., Dove, D. E., Ishiguro, H., Su, Y. R., Brown, A. M., Liu, L., Carter, K. J., Linton, M. F., & Fazio, S. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/hq1101.097798 · Cited by 53 · see citing works
Enhanced ABCG1 expression increases atherosclerosis in LDLr-KO mice on a western diet
Basso, F., Amar, M. J., Wagner, E. M., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.044 · Cited by 53 · see citing works
Wang, M., Franklin, V., Sundaram, M., Kiss, R. S., Ho, K., Gallant, M., & Marcel, Y. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700326200 · Cited by 48 · see citing works
Sviridov, D., Hoang, A., Ooi, E. M. M., Watts, G. F., Barrett, P. H. R., & Nestel, P. J. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.07.007 · Cited by 44 · see citing works
Self-citationSviridov, D., Fidge, N., Beaumier-Gallon, G., et al. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3580079 · Cited by 41 · see citing works
Self-citationEscher, G., Hoang, A., Georges, S., et al. (2004) · Journal of Lipid Research · doi:10.1194/jlr.d400014-jlr200 · Cited by 41 · see citing works
Self-citationCalpe‐Berdiel, L., Rotllán, N., Palomer, X., Ribas, V., Blanco‐Vaca, F., & Escolá‐Gil, J. C. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.11.012 · Cited by 36 · see citing works
Sviridov, D., Fidge, N., Beaumier-Gallon, G., et al. (2001) · Biochemical Journal · doi:10.1042/bj3580079 · Cited by 30 · see citing works
Self-citationThe Role of Different Regions of ATP-Binding Cassette Transporter A1 in Cholesterol Efflux
Mukhamedova, N., Fu, Y., Bukrinsky, M., Remaley, A. T., & Sviridov, D. (2007) · Biochemistry · doi:10.1021/bi700473t · Cited by 24 · see citing works
Self-citationCharacterization of the Maturation of Human Pro-apolipoprotein A-I in an in Vitro Model
Pyle, L. E., Sviridov, D., & Fidge, N. (2001) · Biochemistry · doi:10.1021/bi002025g · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Aho, V., Ollila, H. M., Kronholm, E., Bondia-Pons, I., Soininen, P., Kangas, A. J., Hilvo, M., Seppälä, I., Kettunen, J., Oikonen, M., et al. (2016) · Scientific Reports · doi:10.1038/srep24828 · Cited by 126 · see citing works
Gu, H.-M., Wang, F.-Q., & Zhang, D.-W. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.02.002 · Cited by 39 · see citing works
- Authors
- Mukhamedova, N., Escher, G., D'Souza, W., Tchoua, U., Grant, A., Krozowski, Z., Bukrinsky, M., & Sviridov, D.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- George Washington University (US)
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 49
- Issue
- 11
- Pages
- 2312-2322
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC5475370
- OpenAlex
- W2073185340
- Cited by
- 53
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 8 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 6 · 2012: 6
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fogarty International Center (R03TW006238)
- National Institute of Diabetes and Digestive and Kidney Diseases (R21DK072926)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- apolipoprotein A-I, cholesterol efflux, macrophages, ABCA1, caveolin-1, scavenger receptor class B type I, phospholipid transfer protein, CYP27A1, HDL cholesterol, atherosclerosis, cholesterol export
- MeSH terms
- Animals, Biological Transport, Active, Cell Line, Cholesterol, Lipoproteins, HDL, Macrophages, Signal Transduction, Apolipoprotein A-I, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review