AB0124 EFFECTS OF INHIBITOR K-CARRAGEENAN ON HAECs INFLAMMATORY RESPONSE TO LDLs ISOLATED FROM SLE PATIENTS

Abstract

BackgroundSystemic Lupus Erythematosus (SLE) is an autoimmune disease with a high risk of atherosclerosis and cardiovascular events. It was previously reported by our group that low-density lipoprotein (LDL) particles isolated from SLE patients, during an active state of the disease (‘flare’), promoted an exaggerated inflammatory response in human aortic endothelial cells (HAECs). However, the molecular mechanisms underlying this response still remain elusive.ObjectivesThe hypothesis of this study is that these SLE-LDLs would be using receptor LOX-1, associated with inflammatory conditions and altered lipoproteins, to generate the proatherogenic response in HAECs.MethodsLOX-1 pharmacological inhibitor k-carrageenan was used before the stimulation of HAECs with LDLs isolated from healthy controls (10), non-active (13), or active-SLE patients (13). Gene expression, protein, and cell migration assays were performed to evaluate HAECs inflammatory response.ResultsLOX-1 inhibition with k-carrageenan significantly reduced the expression of vascular cell adhesion molecule 1 (VCAM-1) and restored the gene expression of endothelial nitric oxide synthase (eNOS) in HAECs incubated with non-active SLE LDLs.ConclusionWhile VCAM-1 down-regulation was expected, the immediate next step derived from the observed results will be a deeper understanding of how LOX-1 inhibition may restore the endothelial ability to synthetize NO in the presence of altered LDL. This will allow gaining insight not only on the development of atherosclerosis but also on the clue mechanisms involved in the pathogenesis of SLE.Disclosure of InterestsNone declared