Background/Purpose:

Although the risk of atherosclerotic cardiovascular disease and abnormalities in cholesterol transport have been demonstrated in rheumatoid arthritis (RA), lupus (SLE) and, to a lesser extent, in psoriatic arthritis (PsA), the degree of cholesterol transport abnormalities is not known. This study examines the effect of RA, PsA, and SLE versus healthy control (HC) plasma on cholesterol transport genes. Particular genes affect atherosclerotic processes by modulating cholesterol influx, catabolism, and efflux. Dysfunctional cholesterol handling underlies mechanisms that promote atherosclerosis.

Methods:

THP-1 human macrophages (10⁶/ml) were incubated (18h-24h, RPMI1640 media) in the presence of 10% plasma from patients diagnosed as follows: 8 RA females; 12 SLE (9 female, 3 male), 22 PsA (7 female, 15 male); 21 HC (21 female). Cholesterol transport mRNA was quantified by real-time RT-PCR using specific primers for each gene. Statistical analysis was performed using Graphpad Prism. All data were analyzed by one-way analysis of variance, and pairwise multiple comparisons were made between control and treatment conditions using Bonferroni correction. RA patients fulfilled the 2010 revised criteria of the American College of Rheumatology for classification of RA. SLE patients fulfilled the Systemic Lupus International Collaborating Clinics Classification Criteria of 2012. PsA patients fulfilled the Classification Criteria for Psoriatic Arthritis of 2006. Patients with previous documentation of a diagnosis of a connective tissue disorder other than RA, PsA or SLE were excluded.

Results:

SLE: 10% SLE plasma increased cholesterol influx gene expression. CD36 mRNA increased by 220±56% (P<0.001), LOX-1 by 202±22% (P<0.001), and SR-A1 increased to 122.0±45.0% versus HC plasma (set at 100%). Efflux genes were suppressed. ABCA1 mRNA decreased to 77.0±47.0%, ABCG1 to 89.0±33.0%, and 27-hydroxylase (27-OH) mRNA to 20.0±48.0% versus HC.

RA: 10% RA plasma increased CD36 by 157.4±111.0%, SR-A1 to 124±19.0%, and LOX-1 to 102.0±53.0% versus HC. Mean ABCA1 mRNA decreased to 65.7±28.4 (P<0.001), ABCG1 to 65.0±47.0% (P<0.05), and 27-OH to 32.5±14.2% (P<0.01) in RA treated plasma versus HC plasma.

PsA: 10 % PsA plasma didn’t alter message level of influx nor efflux genes. However, levels of SR-A1 decreased to 80.0±30.0%.

Conclusion:

Consistent with clinic evidence, cholesterol transport abnormalities are most deranged in SLE. RA and SLE plasma induced a consistent pro-atherogenic profile of cholesterol flux genes. PsA plasma was less atherogenic, reflecting their lesser disease-related cardiovascular risk. These results identify cholesterol transport genes as a potential new therapeutic target for atherosclerosis prevention in the setting of autoimmunity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/atherogenic-potency-of-plasma-from-persons-with-autoimmune-rheumatic-disorders-comparative-effects-on-cholesterol-flux-in-human-macrophages/