Proliferation of macrophages due to the inhibition of inducible nitric oxide synthesis by oxidized low-density lipoproteins

Authors

  • Monika Brunner Institute for Physiology, Section for Vegetative Physiology, CEPP, Medical University Vienna, Schwarzspanierstraße 17, 1090 Vienna, Austria
  • Miriam Gruber Institute for Physiology, Section for Vegetative Physiology, CEPP, Medical University Vienna, Schwarzspanierstraße 17, 1090 Vienna, Austria
  • Diethart Schmid Institute for Physiology, Section for Vegetative Physiology, CEPP, Medical University Vienna, Schwarzspanierstraße 17, 1090 Vienna, Austria
  • Halina Baran Institute for Physiology, Section for Vegetative Physiology, CEPP, Medical University Vienna, Schwarzspanierstraße 17, 1090 Vienna, Austria
  • Thomas Moeslinger Institute for Physiology, Section for Vegetative Physiology, CEPP, Medical University Vienna, Schwarzspanierstraße 17, 1090 Vienna, Austria

DOI:

https://doi.org/10.17179/excli2015-151

Keywords:

inducible nitric oxide synthase, lipoproteins, macrophages, atherosclerosis

Abstract

Oxidized low-density lipoprotein (ox-LDL) is assumed to be a major causal agent in hypercholesteraemia-induced atherosclerosis. Because the proliferation of lipid-loaden macrophages within atherosclerotic lesions has been described, we investigated the dependence of macrophage proliferation on the inhibition of inducible nitric oxide synthase (iNOS) by hypochlorite oxidized LDL. Ox-LDL induces a dose dependent inhibition of inducible nitric oxide synthesis in lipopolysaccharide-interferon stimulated mouse macrophages (J774.A1) with concomitant macrophage proliferation as assayed by cell counting, tritiated-thymidine incorporation and measurement of cell protein. Native LDL did not influence macrophage proliferation and inducible nitric oxide synthesis. iNOS protein and mRNA was reduced by HOCl-oxidized LDL (0-40 µg/ml) as revealed by immunoblotting and competitive semiquantitative PCR. Macrophage proliferation was increased by the addition of the iNOS inhibitor L-NAME. The addition of ox-LDL to L-NAME containing incubations induced no further statistically significant increase in cell number. Nitric oxide donors decreased ox-LDL induced macrophage proliferation and nitric oxide scavengers restored macrophage proliferation to the initial values achieved by ox-LDL. The decrease of cytosolic DNA fragments in stimulated macrophages incubated with ox-LDL demonstrates that the proliferative actions of ox-LDL are associated with a decrease of NO-induced apoptosis. Our data show that inhibition of iNOS dependent nitric oxide production caused by hypochlorite oxidized LDL enhances macrophage proliferation. This might be a key event in the pathogenesis of atherosclerotic lesions.

Downloads

Published

2015-03-20

How to Cite

Brunner, M., Gruber, M., Schmid, D., Baran, H., & Moeslinger, T. (2015). Proliferation of macrophages due to the inhibition of inducible nitric oxide synthesis by oxidized low-density lipoproteins. EXCLI Journal, 14, 439–451. https://doi.org/10.17179/excli2015-151

Issue

Vol. 14 (2015)

Section

Original articles

License

Authors who publish in this journal agree to the following terms:

  • The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
  • The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
  • Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
  • The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).