Anzeige

Archive

CD70 limits atherosclerosis and promotes macrophage function

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH16-04-0318
Issue: 2017: Issue 1 2017 (pp. 1-206)
Pages: 164-175
Ahead of Print: 2016-10-27

CD70 limits atherosclerosis and promotes macrophage function

Online Supplementary Material

H. Winkels (1, 2), S. Meiler (1, 2), E. Smeets (2), D. Lievens (1), D. Engel (3), C. Spitz (1), C. Bürger (1), P. Rinne (1), L. Beckers (2), A. Dandl (1), S. Reim (1), M. Ahmadsei (1), J. Van den Bossche (2), L. M. Holdt (4), R. T. A. Megens (1, 3), M. Schmitt (1), M. de Winther (1, 2), E. A. Biessen (3, 5), J. Borst (6), A. Faussner (1), C. Weber (1, 3, 7), E. Lutgens (1, 2), N. Gerdes (1, 2)

(1) Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany; (2) Department of Medical Biochemistry, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands; (3) Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands; (4) Department of Laboratory Medicine, LMU Munich, Munich, Germany; (5) Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen, Aachen, Germany; (6) Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; (7) DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany

Keywords

Atherosclerosis, macrophages, inflammation, CD70

Summary

The co-stimulatory molecule CD70 is expressed on activated immune cells and is known to modulate responses of T, B, and NK cells via its receptor CD27. Until now, there is only limited data describing the role of CD70 in atherosclerosis. We observed that ruptured human carotid atherosclerotic plaques displayed higher CD70 expression than stable carotid atherosclerotic plaques, and that CD70 expression in murine atheroma localized to macrophages. Lack of CD70 impaired the inflammatory capacity (e. g. reactive oxygen species and nitric oxide production) of bone marrow-derived macrophages, increased both M1-like and M2-like macrophage markers, and rendered macrophages metabolically inactive and prone to apoptosis. Moreover, CD70-deficient macrophages expressed diminished levels of scavenger receptors and ABC-transporters, impairing uptake of oxidised low-density lipoprotein (oxLDL) and cholesterol efflux, respectively. Hyperlipidaemic Apoe-/- mice reconstituted with CD70-deficient bone marrow displayed a profound increase in necrotic core size, plaque area, and number of lesional macrophages as compared to mice receiving control bone marrow. Accordingly, 18 week-old, chow diet-fed CD70-deficient Apoe-/- mice displayed larger atheroma characterised by lower cellularity and more advanced plaque phenotype than Apoe-/- mice. In conclusion, CD70 promotes macrophage function and viability and is crucial for effective phagocytosis and efflux of oxLDL. Deficiency in CD70 results in more advanced atheroma. Our data suggest that CD70 mitigates atherosclerosis at least in part by modulating macrophage function.

You may also be interested in...

1.
Didier Hanriot1,2*, Gaëlle Bello1,2*, Armelle Ropars 1,2, Carole Seguin-Devaux 5, Gaël Poitevin 1,2, Sandrine Grosjean 3, Véronique Latger-Cannard2,3,4, Yvan Devaux 1,2, 5, Faiez Zannad 1,2, Véronique Regnault2,4, Patrick Lacolley 1,2, Paul-Michel Mertes 1,2, Ketsia Hess* 1,2, Dan Longrois*1,2

Thromb Haemost 2008 99 3: 558-569

https://doi.org/10.1160/TH07-06-0410

2.
Alexander C. Langheinrich 1, Marian Kampschulte 1, Thomas Buch 1, Rainer M. Bohle²

Thromb Haemost 2007 97 6: 873-879

https://doi.org/10.1160/TH06-12-0742

3.

Pål Aukrust 1,2, Arne Yndestad 1, Camilla Smith 1, Thor Ueland 1,3, Lars Gullestad 4, Jan K. Damås1,2

Thromb Haemost 2007 97 5: 748-754

https://doi.org/10.1160/TH07-01-0029