16/03/2021

LDL lipoproteins behave differently in lupus patients when they have a flare up

A study by two URV-IISPV research groups shows that in patients with a lupus flare up, when artery cells come in contact with LDL lipoproteins, the reaction is similar to arteriosclerosis, which involves a blockage of the arteries. It is shown for the first time that, during flare ups, these lipoproteins cause cells to respond differently and are therefore more dangerous for the arteries

recerca Castro - Ribalta
The research team of the Rovira i Virgili University - Pere Virgili Health Research Institute.

Lupus is an autoimmune disease in which the immune system attacks the body’s own cells and healthy tissues. It mainly affects women, who can present many different symptoms: joint pain, extreme tiredness or fever, and aching muscles, among others. Patients agree that these symptoms appear and remit in the form of flare ups, which can be from mild to aggressive. Knowing what happens during these episodes or indeed why they happen is currently being investigated by scientists from various specialties, all of whom want to improve the lives of patients with this chronic disease.

Patients with lupus are at high risk of cardiovascular problems, although classic risk factors such as blood pressure or cholesterol alter very little. During flare ups the body becomes severely inflamed, which may be one of main influences on the high risk of heart and blood vessel diseases.

Two teams of investigators, the Lipids and Arteriosclerosis Research Unit and the Autoimmunity, Inflammation and Infection Research Group of the URV-IISPV joined forces to study a group of patients at the Hospital Sant Joan de Reus, and collect more information on what happens to arterial cells during flare ups, in this case in relation to cholesterol.

Understanding how cholesterol is deposited in the arteries is important. The problem is not so much the quantity of cholesterol in the blood but, for these patients, the other characteristics of LDL (low-density lipoproteins). These two research teams had already found the size of LDLs and their electrical charge to be more important than the concentration itself. Now they wanted to know if, during a flare-up phase, patients’ lipoproteins had any characteristics that made them more dangerous for the arteries. This study found that they have.

To carry out the study, blood samples were taken from patients while they were in remission, the cholesterol was removed, and the process was repeated when the patients had a flare up. LDLs appeared to be identical in remission and in flare up in terms of concentration, size, and electrical charge. However, when the team carried out an in vitro simulation and brought the cells from the incubated arterial wall into contact with LDL cells at the time of the flare up, the arterial response was typical of those that develop arteriosclerosis.

That is to say, although the composition may be the same and contact with the cells of the arterial wall identical, the behavior of LDL lipoproteins is not the same when there is a flare up as when patients are controlled. “Something makes the cell respond differently and now we need to understand what causes this response,” say Josep Ribalta and Antoni Castro, the researchers responsible for the study.

“Given that these patients have an autoimmune disease and generate antibodies that attack their own tissue, one possibility is that LDLs carry attached parts of these antibodies which cause the artery to have an exaggerated inflammatory response,” they add. Further studies need to be made so that the composition of LDL in flare ups and the role that patients’ arteries play can be better understood.

Bibliographical reference: Rodríguez-Calvo R, Guardiola M, Oliva I, Arrando H, Arranz I, Ferré A, Pellicer P, Parra S, Ribalta J, Castro A. Low-density lipoprotein from active SLE patients is more atherogenic to endothelial cells than low-density lipoprotein from the same patients during remission. Rheumatology (Oxford). 2021 Feb 1;60(2):866-871. doi: 10.1093/rheumatology/keaa380. PMID: 32844232

Reference: Rodríguez-Calvo R, Guardiola M, Oliva I, Arrando H, Arranz I, Ferré A, Pellicer P, Parra S, Ribalta J, Castro A. Low-density lipoprotein from active SLE patients is more atherogenic to endothelial cells than low-density lipoprotein from the same patients during remission. Rheumatology (Oxford). 2021 Feb 1;60(2):866-871. doi: 10.1093/rheumatology/keaa380. PMID: 32844232


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