Understanding how bioactive lipid mediators contribute to vascular dysfunction and target organ damage in systemic lupus erythematosus: A translational opportunity

Systemic Lupus Erythematosus (SLE) predominantly affects women in child-bearing years and is characterised by high risk of cardiovascular disease (CVD) mortality and morbidity.

Target organ damage in SLE patients has a strong vascular component, including hypertension, chronic kidney disease and premature dementia.

We explored plasma lipid profiles in stable SLE patients and found changes indicative of disease-specific molecular mechanisms; moreover, SLE-upregulated lipid species induced small artery endothelial dysfunction when tested on animal arteries.

We hypothesise that accelerated vascular disease in SLE patients is underpinned by altered levels of bioactive lipids causing vascular and endothelial damage.

Our aim is to explore the association between systemic and local levels of bioactive lipids, and vascular dysfunction in SLE, and examine the relevant lipid-mediated molecular mechanisms.

We propose a cross-sectional clinical study to examine vascular dysfunction and its relationship with systemic (plasma) and local (adipose tissue) vasoactive lipid production, assessed by mass spectrometry lipidomics, and gain mechanistic insights using animal tissue to conduct pharmacological studies using myography.

The results will identify lipid species and biochemical pathways linked to vascular damage in SLE, provide mechanistic understanding of their mode of action, and suggest targets to develop CVD treatments for SLE and other autoimmune diseases.