title: Hematopoietic Fas deficiency does not affect experimental atherosclerotic lesion formation despite inducing a proatherogenic state.
abstract: The Fas death receptor (CD95) is expressed on macrophages, smooth muscle cells, and T cells within atherosclerotic lesions. Given the dual roles of Fas in both apoptotic and nonapoptotic signaling, the aim of the present study was to test the effect of hematopoietic Fas deficiency on experimental atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr(-/-)). Bone marrow from Fas(-/-) mice was used to reconstitute irradiated Ldlr(-/-) mice as a model for atherosclerosis. After 16 weeks on an 0.5% cholesterol diet, no differences were noted in brachiocephalic artery lesion size, cellularity, or vessel wall apoptosis. However, Ldlr(-/-) mice reconstituted with Fas(-/-) hematopoietic cells had elevated hyperlipidemia [80% increase, relative to wild-type (WT) controls; P < 0.001] and showed marked elevation of plasma levels of CXCL1/KC, CCL2/MCP-1, IL-6, IL-10, IL-12 subunit p70, and soluble Fas ligand (P < 0.01), as well as systemic microvascular inflammation. It was not possible to assess later stages of atherosclerosis because of increased mortality in Fas(-/-) bone marrow recipients. Our data indicate that hematopoietic Fas deficiency does not affect early atherosclerotic lesion development in Ldlr(-/-) mice.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: R Angelo
authors.initials: RA
authors.lastname: de Claro
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tang
authors.forename: Vicki
authors.initials: V
authors.lastname: Morgan-Stevenson
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Schwartz
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwata
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Raines
authors.forename: John M
authors.initials: JM
authors.lastname: Harlan
mesh_terms: D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000150:complications / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D002678:Chimera; D004195:Disease Models, Animal; D006413:Hematopoietic System / Q000378:metabolism* / Q000473:pathology*; D006937:Hypercholesterolemia / Q000150:complications / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000473:pathology; D051379:Mice; D055806:Microvessels / Q000473:pathology; D011973:Receptors, LDL / Q000172:deficiency / Q000378:metabolism; D019014:fas Receptor / Q000172:deficiency* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018925:Chemokines; C491899:Fas protein, mouse; D011973:Receptors, LDL; D019014:fas Receptor