Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Atherogenic Properties of Rheumatoid Arthritis Plasma: Effect on Cholesterol Transport Genes.
Reiss1, Allison B., Voloshyna1, Iryna, Littlefield1, Michael, Belilos1, Elise, Belostocki2, Kristina, Bonetti1, Lois A., Rosenblum1, Gary C.
The risk of cardiovascular (CV) morbidity and mortality is profoundly increased in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We have reported that SLE patients manifest a pattern of disturbance in expression of genes involved in lipid transport that is atheroma-promoting. When THP-1 human monocytes/macrophages are exposed to lupus plasma, the cholesterol efflux proteins 27-hydroxylase (27-OHase) and ATP binding cassette transporter (ABC)A1 are suppressed while the scavenger receptor CD36 that facilitates cholesterol uptake is augmented, leading to cholesterol overload and foam cell formation (FCF). This study examines whether RA patients exhibit comparably atherogenic plasma. In addition to the genes already mentioned, we look at the nuclear hormone receptor liver X receptor (LXR), which stimulates cholesterol efflux and induces expression of ABC transporters.
CD36, ABCA1, 27-OHase and LXR expression were evaluated in THP-1 human monocytes and human aortic endothelial cells (HAEC), cell types relevant to atherogenesis. Cells were incubated for 18h and 24h in medium containing 0, 10 or 25% of either RA patient plasma or normal human plasma (NHP). Following the 18h incubation, mRNA was isolated and reverse transcribed. The resulting cDNA was subjected to quantitative PCR using specific primers for each gene. Cellular extracts were prepared for Western immunoblotting after 24h.
Pooled plasma from RA patients in this study population was compared to NHP. The presence of 10% RA plasma upregulated CD36 message by 270.8 ± 88.0% in HAEC (n=3, P<0.001) above NHP (Figure 1).
In THP-1 and HAEC, 27-OHase message level fell by 46.23 ± 12.5% and 69.1 ± 4.12% (Figure 2A) (n=3, P<0.001) below NHP, respectively and ABCA1 fell by 50.6 ± 15.0% (n=3, P<0.001) and 45.6 ± 8.7% (Figure 2B) (n=3, P<0.01) below NHP, respectively. LXR levels fell concomitantly: by 26.6 ± 3.9% and 56.6 ± 7.4%% (n=3, P<0.001) below NHP, respectively. Western blot analysis confirmed PCR results.
Traditional CV risk assessment is inadequate in RA. This study demonstrates pro-atherogenic properties of RA plasma that may promote atherosclerosis by increasing vulnerability to cholesterol overload. Demonstration of disrupted cholesterol homeostasis in this select group of patients provides further evidence of the involvement of the immune system in atherogenesis. Our findings may lead to the use of a cholesterol transport gene profile for evaluation of CV risk in this susceptible population.
To cite this abstract, please use the following information:
Reiss, Allison B., Voloshyna, Iryna, Littlefield, Michael, Belilos, Elise, Belostocki, Kristina, Bonetti, Lois A., et al; Atherogenic Properties of Rheumatoid Arthritis Plasma: Effect on Cholesterol Transport Genes. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1072