Atherosclerosis in Rheumatoid Arthritis and Lupus: Restoring Cholesterol Balance
Hypothesis: SLE and RA increase risk of myocardial infarction (MI, heart attack). Immune reactants in the circulation of SLE patients downregulate cholesterol efflux proteins 27-hydroxylase and ABCA1 and upregulate scavenger receptor CD36, thus encouraging cholesterol accumulation. Adenosine A2A receptor agonist or statin treatment of cells exposed to SLE plasma (or immune complexes or cytokine-enriched plasma fractions from SLE patients) may ameliorate inflammatory properties of their plasma, lessening its atherogenic potency.
Rationale: SLE and RA plasma contain components not present in significant levels in normal plasma that could, individually or acting together, affect 27-hydroxylase, ABCA1 and CD36 expression. Candidate components include autoantibodies, immune complexes, and various cytokines. Statins reduce major cardiovascular events and death. Modulation of adenosine signaling participates in regulation of 27-hydroxylase and ABCA1. As a potential preventative and therapeutic approach to atherosclerotic cardiovascular disease, the investigators evaluate the effect of A2A receptor agonists and statins on atherogenic parameters in SLE and RA plasma.
Experimental Plan: Quantitate 27-hydroxylase and several other proteins involved in cellular cholesterol uptake and excretion in THP-1 monocytes/macrophages and HAEC after exposure to plasma and plasma components from SLE patients (and controls) ± lipid loading with acetylated LDL with/without addition of A2AR agonist, statin, or both. Determine relative impact of immune complexes and cytokines on expression of proteins involved in cholesterol flux. Determine levels of proteins involved in cellular cholesterol influx/efflux in peripheral blood mononuclear cells isolated from RA, SLE and psoriatic arthritis patients and normal controls at baseline, then following incubation in culture media alone or with statin, adenosine A2A agonist or both statin + A2AR agonist.
|Study Design:||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Official Title:||Atherosclerosis in RA and Lupus: Restoring Cholesterol Balance|
- Comparison of 27-hydroxylase level in THP-1 monocytes incubated in human plasma (RA patient, SLE, normal control, psoriatic arthritis). [ Time Frame: 3 years ] [ Designated as safety issue: No ]The activated proinflammatory state of monocytes in RA and SLE subjects constitutes a novel parameter of risk associated with this disorder, related to altered expression of cholesterol transport genes. 27-hydroxylase level may be diminished by the plasma of patents with autoimmune rheumatic disorders.
- Plasma 27-hydroxycholesterol levels. [ Time Frame: 3 years ] [ Designated as safety issue: No ]Plasma 27-hydroxycholesterol may be lower in RA and SLE patients than in healthy controls due to less 27-hydroxylase expression and activity in RA and lupus.
Biospecimen Retention: Samples Without DNA
|Study Start Date:||September 2008|
|Estimated Study Completion Date:||November 2013|
|Estimated Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
Active SLE patients
Age 18-65; female and male. No methotrexate or statin therapy in prior 3 months. Not on biological therapies. Fulfill 1982 ACR revised criteria for SLE. SLE activity status designated using the SLEDAI disease activity index. Patients excluded if previous documentation of a connective tissue disorder other than SLE.
Age 18-65; female and male. No methotrexate or statin therapy in prior 3 months. Not on biological therapies. Diagnosed according to criteria described by McGonagle et al (McGonagle, D., Conaghan, P.G., and Emery, P. Psoriatic arthritis: a unified concept twenty years on. Arthritis Rheum 1999; 42: 1080-1086.)
Age 18-65; female and male. No methotrexate or statin therapy in prior 3 months. Not on biological therapies. Healthy volunteers. Not on corticosteroids.
Active RA patients
Age 18-65, male and female, no methotrexate or statin therapy in prior 3 months. Not on biological therapies. satisfy at least 4 of the 7 revised criteria (1987) for the classification of RA
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|Contact: Allison B Reiss, MDfirstname.lastname@example.org|
|United States, New York|
|Winthrop University Hospital||Recruiting|
|Mineola, New York, United States, 11501|
|Contact: Steven Carsons, MD 516-663-4751 SCarsons@winthrop.org|
|Principal Investigator: Allison B Reiss, MD|
|Sub-Investigator: Steven Carsons, MD|
|Principal Investigator:||Allison B Reiss, MD||Winthrop University Hospital|