Antibodies to adult human endothelial cells cross-react with oxidized low-density lipoprotein and beta 2-glycoprotein I (beta 2-GPI) in systemic lupus erythematosus.
ABSTRACT Cardiovascular manifestations are common in systemic lupus erythematosus (SLE). Oxidized low-density lipoprotein (oxLDL) is implicated in cardiovascular disease, especially atherosclerosis, and cross-reacts with antibodies to cardiolipin (aCL). beta 2-GPI is a plasma protein participating in the coagulating cascade, and is also cofactor for aCL, and some aCL have been shown to be directed against beta 2-GPI and/or complexes between beta 2-GPI and phospholipids. Lysophosphatidylcholine (LPC) is a phospholipid present both in oxLDL and in damaged endothelium, and we recently showed that LPC is involved in the antigenicity of oxLDL. Antibodies to endothelial cells (aEC) correlate with diseases activity in SLE and vasculitis, and we recently showed that aEC are enhanced in cardiovascular disease such as borderline hypertension and early atherosclerosis. aEC were determined using EC from adult V. Saphena Magna. Antibody levels were determined by ELISA. aEC of IgG type were enhanced in 184 patients with SLE compared with 85 healthy controls. There was a close correlation between aoxLDL, aCL, aLPC, a beta 2-GPI and aEC. Binding of sera to EC was competitively inhibited by beta 2-GPI, LPC and oxLDL. Taken together, the data indicate that EC share antigenic epitopes with beta 2-GPI and with oxLDL, especially LPC. Phospholipids in EC membranes may thus be antigenic epitopes. beta 2-GPI may bind to these phospholipids, and become an autoantigen. LPC is formed by oxidation of phospholipids and/or proinflammatory factors leading to activation of phospholipase A2, and the findings indicate the potential role of both lipid oxidation and phospholipase A2 in SLE.
Full-textDOI: · Available from: Liselotte Schäfer Elinder, Jun 02, 2015
SourceAvailable from: Lakshmi Mundkur[Show abstract] [Hide abstract]
ABSTRACT: Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.Cholesterol 08/2012; 12. DOI:10.1155/2012/571846
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ABSTRACT: With improved control of the immunological phenomena of systemic lupus erythematosus, the epidemiology of this disease is changing. While both cardiac and neurological manifestations of systemic lupus erythematosus have been consistently described, there is increasing awareness of the need for general cardiovascular prevention in systemic lupus erythematosus. An excess of stroke is seen in systemic lupus erythematosus especially, in those cases with anticardiolipin antibodies. There is increasing evidence for the contributory role of other cardiovascular risk-factors, including hypertension, hyperlipidemia and inflammatory markers, to the epidemiology of stroke and recognition of the role of endothelial dysfunction may play in systemic lupus erythematosus. Therapeutic approaches currently rely on anticoagulation alone. This review suggest that the full panoply of stoke interventions, including antihypertensive therapy and lipid-lowering, should be applied in the case of stroke in systemic lupus erythematosus just as in atherosclerotic stroke.Expert Review of Neurotherapeutics 05/2002; 2(3):385-90. DOI:10.1586/1473718.104.22.1685 · 2.83 Impact Factor