Decreased binding of annexin v to endothelial cells: a potential mechanism in atherothrombosis of patients with systemic lupus erythematosus.
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.
Cederholm
Anna
A
Department of Medicine, Center for Infectious Medicine, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden. anna.cederholm@medhs.ki.se
Svenungsson
Elisabet
E
Jensen-Urstad
Kerstin
K
Trollmo
Christina
C
Ulfgren
Ann-Kristin
AK
Swedenborg
Jesper
J
Fei
Guo-Zhong
GZ
Frostegård
Johan
J
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
D017304:Annexin A5; D002308:Cardiolipins; D007074:Immunoglobulin G