title: Vulnerability of atherosclerotic plaques is associated with type I interferon in a murine model of lupus and atherosclerosis.
abstract: This study aimed to investigate the relationship between type I interferon (IFN-I) and plaque stability in pristane-treated apolipoprotein E-knockout (ApoE(-/-)) mice. Antinuclear antibody (ANA) and extractable nuclear antigen antibody (ENA) levels were measured by immunofluorescence and enzyme-linked immunospot assay. Atherosclerotic plaques were detected by Sirius red/fast green staining. Cell apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling. Gene expression was determined by real-time PCR analyses. We found that pristane-treated ApoE(-/-) mice developed a lupus-like syndrome characterized by an increased production of serum ANA and ENA. Pristane treatment decreased the collagen content and increased the number of apoptotic cells in plaques. Moreover, IFN-induced ISG15, IFIT1-1, and IFIT1-2 gene expression was increased in peripheral blood cells and aortic plaques. An IFN-α-stimulated macrophage supernatant inhibited collagen type I, alpha 1 gene expression in vascular smooth muscle cells. We concluded that the vulnerability of plaques was associated with the activation of IFN-I in pristane-treated ApoE(-/-) mice. Thus, we speculated that the higher prevalence of cardiovascular events in patients with systemic lupus erythematosus could be due to plaque instability.
authors.affiliation: Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: B
authors.initials: B
authors.lastname: Qu
authors.affiliation: Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Rheumatology, Shanghai, China yijiangdf@163.com.
authors.forename: C D
authors.initials: CD
authors.lastname: Bao
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D016898:Interferon-alpha