Bioactive lipids and vascular function in systemic lupus erythematosus
Research type
Research Study
Full title
Understanding how bioactive lipid mediators contribute to vascular dysfunction and target organ damage in systemic lupus erythematosus: a translational opportunity
IRAS ID
286730
Contact name
Anna Nicolaou
Contact email
Sponsor organisation
The University of Manchester
Duration of Study in the UK
2 years, 11 months, 31 days
Research summary
Systemic Lupus Erythematosus (SLE) is a long-term illness that mainly affects younger women. Women with SLE have higher risk of developing heart and blood vessel disease and often die prematurely. Damage to the arteries in various organs can lead to increased blood pressure, kidney disease and early dementia. We looked at specialist molecules (lipid mediators) present in blood and found their profiles were altered in patients with SLE. We also examined their activity on arteries isolated from animals and found that they can damage the way these arteries constrict and relax. This suggests that altered production of lipid mediators in SLE can be responsible for arterial disease. To explore this finding, we will perform a clinical study with SLE patients and examine the dysfunction of their arteries and the lipid mediators found in their blood and the fat tissue that surrounds and protects their blood vessels. We will recruit volunteers (18-70) with SLE from the Kellgren Rheumatology clinic, and healthy volunteers from local advertisements. Participants will attend clinic visits where they will undergo a robust assessment of cardiovascular function (blood pressure, arterial stiffness, arterial function, cardiac perfusion MRI), as well as donating blood, urine and adipose tissue samples. These samples will be used for routine assessment of SLE and cardiovascular disease markers, as well as quantitation of circulating and local bioactive lipids. Our results will help us get a detailed understanding of the pathways and lipid mediators that are involved in blood vessel damage in SLE, and help us to plan and design new treatments.
Results lay summary:
We looked at specialist molecules (bioactive lipids and lipid mediators) present in the blood and skin of female Systemic Lupus Erythematosus (SLE) patients (n=33), and healthy controls (n=23). We found that levels of various bioactive lipid mediators were significantly affected by the disease; these were linoleic acid (LA)-derived octadecanoids (EpOMEs, DiHOMEs and HoDEs), dihydroceramides, ceramides, triglycerides, sphingomyelins, phosphatidylcholine (PC) plasmalogens and phosphatidylethanolamine (PE) plasmalogens. We also took clinical measures of vascular and endothelial health, and profiled blood microvesicle subpopulations to obtain additional measure of vascular damage, as circulating levels of endothelial-derived and platelet-derived microvesicles have been associated with endothelial damage and vascular dysfunction in SLE. Finally, we measured myocardial function, using cardiovascular magnetic resonance perfusion imaging (pCMR) to provide visual and, for the first time, quantitative assessment of myocardial microvascular function in SLE patients with no known cardiac involvement. This test will complement the clinic measures of vascular health and generate baseline readings of endothelial dysfunction in SLE patients. We are now in the process of performing correlations between bioactive lipid levels in blood and skin, and clinical measures of vascular and endothelial health. Overall, the study findings will provide insight into the potential role of bioactive lipid in the vascular damage and high risk of cardiovascular disease observed in SLE.REC name
North West - Greater Manchester West Research Ethics Committee
REC reference
20/NW/0429
Date of REC Opinion
14 Dec 2020
REC opinion
Further Information Favourable Opinion