; Langmann, Thomas ; Wolf, Zsuzsanna ; Weiss, Thomas S.
; Groitl, Peter ; Dobner, Thomas ; Kasprzak, Piotr M. ; Göbölös, Laszlo ; Falkert, Andreas ; Seelbach-Goebel, Birgit ; Gellhaus, Alexandra ; Winterhager, Elke ; Schmidt, Markus ; Semenza, Gregg L. ; Schmitz, Gerd 
| Dokumentenart: | Artikel | ||||||
|---|---|---|---|---|---|---|---|
| Open Access Art: | Kein Open Access | ||||||
| Titel eines Journals oder einer Zeitschrift: | The International Journal of Biochemistry & Cell Biology | ||||||
| Verlag: | PERGAMON-ELSEVIER SCIENCE LTD | ||||||
| Ort der Veröffentlichung: | OXFORD | ||||||
| Band: | 42 | ||||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 2 | ||||||
| Seitenbereich: | S. 241-252 | ||||||
| Datum: | 12 Oktober 2009 | ||||||
| Institutionen: | Medizin > Lehrstuhl für Chirurgie Medizin > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medizin > Abteilung für Thoraxchirurgie Medizin > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medizin > Lehrstuhl für Medizinische Mikrobiologie und Hygiene | ||||||
| Sonstige Projekte: | DFG SFB Transregio-13 Project | ||||||
| Identifikationsnummer: |
| ||||||
| Stichwörter / 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 | ||||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||||
| Status: | Veröffentlicht | ||||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||||
| An der Universität Regensburg entstanden: | Zum Teil | ||||||
| Dokumenten-ID: | 59071 |
Zusammenfassung
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 ...

Zusammenfassung
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.
Metadaten zuletzt geändert: 05 Dez 2024 09:49
Altmetric