Basic Research in Cardiology

, 106:761 | Cite as

OxLDL and macrophage survival: essential and oxygen-independent involvement of the Hif-pathway

  • David M. PoitzEmail author
  • Antje Augstein
  • Sönke Weinert
  • Rüdiger C. Braun-Dullaeus
  • Ruth H. Strasser
  • Alexander Schmeisser
Original Contribution


Atherosclerotic plaques are characterized by hypoxic even anoxic areas and by high concentrations of oxidized lipoproteins. Moreover, unstable plaques attract a high number of macrophages despite the proapoptotic background within these plaques. Recently, it was shown that these macrophages are positive for Hif-1α. This subunit is a part of hypoxia-inducible factor 1 (Hif-1), a key transcriptional factor under hypoxia. Till date, it is not understood whether the Hif-system (consisting of Hif-1, Hif-2 and Hif-3) is involved in protection of macrophages under these proatherogenic conditions. The present study delineates that oxLDL causes fundamental changes in the regulation of the Hif-system in primary human macrophages. First, both oxLDL and hypoxia mediate accumulation of Hif-1α protein. Second, treatment with a combination of oxLDL and hypoxia is acting in an additive manner on Hif-1α protein content. Third, oxLDL alone does not increase Hif-2α protein, but abolishes the hypoxic induction of Hif-2α completely. OxLDL treatment alone was not toxic for macrophages under neither normoxia nor hypoxia. But, inhibition of Hif-pathway by adenoviral expression of a dominant-negative mutant combined with oxLDL treatment independently of the oxygen tension leads to apoptosis, as determined by caspase-3 activation and induction of DNA fragmentation. Furthermore, this inhibition also mediates the opening of the mitochondrial permeability transition pore. In conclusion, the present data show that Hif-1α regulation is essential for survival of oxLDL-treated macrophages independent of the oxygen tension. Therefore, this newly characterized mechanism might also have an important influence for the vulnerability of atherosclerotic plaques.


Macrophages OxLDL Hypoxia-inducible factors Apoptosis 



R.B.-D. was supported by grants of the SFB 655. This project was also supported by grants of the MedDrive program and the CRTD. Anita Männel and Peggy Barthel are acknowledged for excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • David M. Poitz
    • 1
    Email author
  • Antje Augstein
    • 1
  • Sönke Weinert
    • 1
    • 2
  • Rüdiger C. Braun-Dullaeus
    • 1
    • 2
  • Ruth H. Strasser
    • 1
  • Alexander Schmeisser
    • 1
    • 2
  1. 1.Department of Internal Medicine and CardiologyUniversity of Technology DresdenDresdenGermany
  2. 2.Internal Medicine, Department of Cardiology, Angiology and PneumologyMagdeburg UniversityMagdeburgGermany

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