Ugocsai, Peter and Hohenstatt, Antonia and Paragh, Gyoergy and Liebisch, Gerhard and Langmann, Thomas and Wolf, Zsuzsanna and Weiss, Thomas and Groitl, Peter and Dobner, Thomas and Kasprzak, Piotr and Goeboeloes, Laszlo and Falkert, Andreas and Seelbach-Goebel, Birgit and Gellhaus, Alexandra and Winterhager, Elke and Schmidt, Markus and Semenza, Gregg L. and Schmitz, Gerd (2010) HIF-1beta determines ABCA1 expression under hypoxia in human macrophages. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 42 (2). pp. 241-252. ISSN 1357-2725, 1878-5875
Full text not available from this repository. (Request a copy)Abstract
ATP-binding cassette transporter A1 plays (ABCA1) a major role in reverse cholesterol transport, a process closely related to atherogenesis. In the thickening atherosclerotic lesions lipid loaded macrophages are exposed to regions of local hypoxia that may influence reverse cholesterol transport. Here we studied the effect of hypoxia on ABCA1 regulation and cholesterol efflux in human macrophages. We found that the hypoxia-inducible factor 1 (HIF-1) specifically binds to the HIF-1 response element of the ABCA1 promoter and the HIF-1 complex increases ABCA1 promoter activity along with ABCA1 expression. Primary human macrophages exposed to hypoxia or expressing constitutively active HIF-1 alpha responded with a potent change in ABCA1 expression, which showed a strong correlation with HIF-1 beta expression (r: 0.95-0.91). Moreover, ABCA1-mediated cholesterol efflux was also found to be regulated by HIF-1 beta under hypoxia. In vivo, in macrophages prepared from human atherosclerotic lesions ABCA1 levels showed a strong correlation with HIF-1 beta expression. This in vivo regulatory mechanism was confirmed in human pre-eclamptic placentas, a clinical condition with severe local hypoxia. These results demonstrate that HIF-1beta availability determines ABCA1 expression and cholesterol efflux in macrophages under hypoxia and may contribute to the interpersonal variability of atherosclerotic lesion progression. (C) 2009 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ATP-BINDING CASSETTE; INDUCIBLE FACTOR-I; TRANSPORTER A1; KNOCKOUT MICE; TANGIER-DISEASE; FACTOR 1-ALPHA; APOA-I; PATHWAY; GENE; ATHEROSCLEROSIS; ABCA1; Hypoxia; HIF-1; Macrophages; Atherosclerosis; Cholesterol efflux |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Abteilung für Thoraxchirurgie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Aug 2020 06:05 |
| Last Modified: | 10 Aug 2020 06:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25219 |
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