title: CD70 limits atherosclerosis and promotes macrophage function.
abstract: 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.
authors: Holger
authors: H
authors: Winkels
authors: Svenja
authors: S
authors: Meiler
authors: Esther
authors: E
authors: Smeets
authors: Dirk
authors: D
authors: Lievens
authors: David
authors: D
authors: Engel
authors: Charlotte
authors: C
authors: Spitz
authors: Christina
authors: C
authors: Bürger
authors: Petteri
authors: P
authors: Rinne
authors: Linda
authors: L
authors: Beckers
authors: Angelika
authors: A
authors: Dandl
authors: Sigrid
authors: S
authors: Reim
authors: Maiwand
authors: M
authors: Ahmadsei
authors: Jan
authors: J
authors: Van den Bossche
authors: Lesca M
authors: LM
authors: Holdt
authors: Remco T A
authors: RT
authors: Megens
authors: Martin
authors: M
authors: Schmitt
authors: Menno
authors: M
authors: de Winther
authors: Eric A
authors: EA
authors: Biessen
authors: Jannie
authors: J
authors: Borst
authors: Alexander
authors: A
authors: Faussner
authors: Christian
authors: C
authors: Weber
authors: Esther
authors: E
authors: Lutgens
authors: Norbert Gerdes, PhD, Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Pettenkoferstrasse 9, 80336 Munich, Germany, Tel.: +49 89 4400 54672, Email: norbert.gerdes@med.uni-muenchen.de.
authors: Norbert
authors: N
authors: Gerdes
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D016026:Bone Marrow Transplantation; D053282:CD27 Ligand / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000074085:Mice, Knockout, ApoE; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D053282:CD27 Ligand; C505771:CD70 protein, human; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; D002784:Cholesterol
keywords: Atherosclerosis; CD70; inflammation; macrophages