title: Decreased binding of annexin v to endothelial cells: a potential mechanism in atherothrombosis of patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  The cause of the exceedingly high risk of atherothrombosis in systemic lupus erythematosus (SLE) is not clear but antiphospholipid antibodies (aPL) and potentially antithrombotic annexin V have been implicated.
  
  
  RESULTS
  Twenty-six women (52+/-8.2 years) with SLE and a history of cardiovascular disease (CVD) (SLE cases) were compared with 26 women with SLE but no CVD (SLE controls) and 26 healthy women (population controls). Common carotid intima-media thickness (IMT) was determined by B-mode ultrasound as a surrogate measure of atherosclerosis. Annexin V binding to human umbilical vein endothelial cells (HUVECs) as determined by flow cytometry after 24-hour culture with plasma was decreased when plasma from SLE cases was used (SLE cases versus population controls: P=0.002; SLE cases versus SLE controls P=0.02). Antibodies against cardiolipin were among IgG antibodies causing decreased binding. There was a positive association between annexin V binding and IMT (R=0.73; P<0.001) among SLE cases. Immunohistochemical analysis revealed presence of annexin V in all human atherosclerotic plaques tested, especially at sites prone to rupture.
  
  
  CONCLUSIONS
  Decreased annexin V binding to endothelium caused by antibodies may represent a novel mechanism of atherothrombosis. We hypothesize that even though annexin V may promote plaque growth at some disease stages, it may also stabilize plaque.
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden. anna.cederholm@medhs.ki.se
authors.forename: Anna
authors.initials: A
authors.lastname: Cederholm
authors.forename: Elisabet
authors.initials: E
authors.lastname: Svenungsson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jensen-Urstad
authors.forename: Christina
authors.initials: C
authors.lastname: Trollmo
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Ulfgren
authors.forename: Jesper
authors.initials: J
authors.lastname: Swedenborg
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Fei
authors.forename: Johan
authors.initials: J
authors.lastname: Frostegård
mesh_terms: D017304:Annexin A5 / Q000276:immunology / Q000378:metabolism*; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D002308:Cardiolipins / Q000276:immunology / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000473:pathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism / Q000633:toxicity; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications*; D008875:Middle Aged; D011485:Protein Binding; D013194:Staining and Labeling / Q000379:methods; D013927:Thrombosis / Q000209:etiology*; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography; D014471:Umbilical Veins / Q000378:metabolism / Q000473:pathology
chemical_list: D017304:Annexin A5; D002308:Cardiolipins; D007074:Immunoglobulin G