on November 11, 2004
Published online before print November 11, 2004, doi: 10.1161/01.ATV.0000150415.18759.36
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Submitted on May 13, 2004
Accepted on October 28, 2004
Decreased Binding of Annexin V to Endothelial Cells. A Potential Mechanism in Atherothrombosis of Patients With Systemic Lupus Erythematosus
Anna Cederholm *;
From the Department of Medicine (A.C., G.-Z.F., J.F.), CIM and CME, Karolinska University Hospital, Huddinge; the Department of Medicine (E.S., C.T., A.-K.U.), Rheumatology Unit and CMM, Karolinska University Hospital, Solna; the Department of Clinical Physiology (K.J.-U.), Södersjukhuset; Department of Surgery (J.S.), Karolinska University Hospital, Huddinge; and the Karolinska Institutet (A.C., E.S., K.J.-U., C.T., A.-K.U., J.S., G.-Z.F., J.F.), Stockholm, Sweden.
* To whom correspondence should be addressed. E-mail: anna.cederholm{at}medhs.ki.se.
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.
Methods and 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 autoantibodies 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.
Key words: systemic lupus erythematosus • atherothrombosis • atherosclerosis • annexin V • antibodies
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