Annexin A5 in cardiovascular disease and systemic lupus erythematosus.
Atherosclerosis, a major cause of disease and death from cardiovascular disease (CVD), is an inflammatory disease characterized by T cell and monocyte/macrophage infiltration in the intima of large arteries. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in systemic lupus erythematosus (SLE), often considered a prototypic autoimmune disease. A combination of traditional and non-traditional risk factors, including dyslipidemia, inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. aPL are highly thrombogenic, and possible mechanisms include direct effects of aPL on endothelial and other cells, and interference with coagulation reactions. More than a thousand proteins of the annexin-superfamily are expressed in eukaryotes. Annexins are ubiquitous, highly conserved, predominantly intracellular proteins, widely distributed in tissues. Annexin A5 (ANXA5) is an important member of the annexin family due to its antithrombotic properties. These are believed to be caused by it forming a two-dimensional protective shield, covering exposed potentially thrombogenic cell surfaces. Recently, ANXA5 has been implicated in SLE since aPL interfere with ANXA5 binding to placental trophoblasts, causing microthrombosis and miscarriage, a rather common complication in SLE. We recently demonstrated that ANXA5 may play a role in CVD and is abundant in late-stage atherosclerotic lesions. Sera from SLE-patients with a history of CVD inhibited ANXA5 binding to endothelium, caused by IgG antibodies, to a significant degree aPL. This review will focus on potential involvement of ANXA5 in pathogenesis of CVD, particularly caused by underlying atherosclerosis and atherothrombosis.
Cederholm
Anna
A
Center for Infectious Medicine and Unit of Rheumatology, F59, Department of Medicine, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden. anna.cederholm@medhs.ki.se
Frostegård
Johan
J
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism*; D017152:Antibodies, Antiphospholipid / Q000276:immunology; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000378:metabolism*
D017304:Annexin A5; D017152:Antibodies, Antiphospholipid; D005343:Fibrinolytic Agents