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Antiphospholipid antibodies induce vascular functional changes in mice: a mechanism of vascular lesions in antiphospholipid syndrome?

INSERM U644 and Institute for Biomedical Research, IFRMP 23, Rouen University Medical School, Rouen Cedex, France; Department of Internal Medicine, Rouen University Hospital, Rouen Cedex, France

A Lartigue

INSERM U519 and Institute for Biomedical Research, IFRMP 23, Rouen University Medical School, Rouen Cedex, France

J Favre

INSERM U644 and Institute for Biomedical Research, IFRMP 23, Rouen University Medical School, Rouen Cedex, France

D Gilbert

INSERM U519 and Institute for Biomedical Research, IFRMP 23, Rouen University Medical School, Rouen Cedex, France

F Tron

INSERM U519 and Institute for Biomedical Research, IFRMP 23, Rouen University Medical School, Rouen Cedex, France

H Lévesque

INSERM U644 and Institute for Biomedical Research, IFRMP 23, Rouen University Medical School, Rouen Cedex, France; Department of Internal Medicine, Rouen University Hospital, Rouen Cedex, France

C Thuillez

INSERM U644 and Institute for Biomedical Research, IFRMP 23, Rouen University Medical School, Rouen Cedex, France

V Richard

INSERM U644 and Institute for Biomedical Research, IFRMP 23, Rouen University Medical School, Rouen Cedex, France

Abstract

A premature atherosclerosis has been presumed in patients with antiphospholipid syndrome. The potential role of antiphospholipid antibodies in the development of atheroma is rather controversial. In this study, we tested the hypothesis that antiphospholipid antibodies could induce atherosclerosis via vascular functional changes. CD1 mice received one single injection of antiphospholipid monoclonal antibodies derived from male (BXSB × NZW) F1 mice with a lupus-like disease associated with an antiphospholipid syndrome and coronary artery disease. One week later, first-order mesenteric arteries (diameter 220–260 µm) were isolated and mounted on a small-vessel myograph for the measurement of the relaxation responses to acetylcholine or the NO donor nitroprusside after precontraction by phenylephrine. Five out of eight antiphospholipid monoclonal antibodies reduced the response to acetylcholine compared with control mice, and this effect was especially marked with one of them. No change in the response to nitroprusside was observed. The impairment was maintained after 3 weeks of treatment and appeared related to a moderate decrease in NO-mediated responses and a marked decrease in prostanoid-mediated relaxations. These vascular functional changes could be prevented by chronic treatment with statins or aspirin. These data could constitute additional elements supporting a direct pathogenic role of antiphospholipid antibodies. We suggest that a sub-population of these autoantibodies could be responsible for the endothelial dysfunction observed in antiphospholipid syndrome.

Key Words: antiphospholipid • vascular functional changes • atherosclerosis

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