Abstract 862: Plasma Asymmetric Dimethylarginine is Elevated and Related to Endothelial Progenitor Cells Depletion and Carotid Intima-Media Thickness in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is associated with accelerated atherogenesis. Similarities between RA and atherosclerosis include endothelial dysfunction and depletion of bone marrow-derived endothelial progenitor cells (EPC) in blood. Endothelial dysfunction, EPC depletion and elevated circulating endogenous inhibitor of nitric oxide (NO) synthesis (asymmetric dimethylarginine, ADMA) are predictors of major adverse cardiovascular (CV) events in coronary artery disease. We assessed the hypothesis that abnormal plasma ADMA may be linked to EPC depletion and subclinical atherosclerosis in RA.
Methods: We studied 30 patients (25 women, 5 men; age: 47 ±12 years) with active RA (disease activity score > 3.2; disease duration: 5±4 years). Exclusion criteria were clinically evident atheroclerosis, age > 60 years, hypertension, hyperlipidemia, diabetes, body mass index > 30 kg/m2, creatinine clearance < 60 ml/min and any CV medication. L-arginine, ADMA and symmetric dimethylarginine (SDMA) in plasma were measured with liquid chromatography/mass spectrometry. EPC number in blood was assayed by flow cytometry and expressed as a percentage of CD34/KDR (kinase-insert domain receptor) double-positive cells in the lymphocytic gate. Mean intima-media thickness of the common carotid arteries (IMT) was measured by B-mode ultrasound.
Results: As compared to 20 controls matched for age and sex, in RA we found elevated ADMA (0.49±0.07 vs. 0.40±0.07 μmol/l for RA and controls, respectively, p<0.001) and lower EPC number (0.03±0.02 vs. 0.06±0.03 %, p<0.05). There were no intergroup differences in L-arginine (69±19 vs. 63±16 μmol/l, p=n.s.) or SDMA (0.42±0.08 vs. 0.41±0.06 7mu;mol/l, p=n.s.). In RA EPC count correlated inversely with ADMA (r = -0.41, p=0.05) being unrelated to SDMA (r = 0.14, p=n.s.). In multiple regression IMT was positively linked to age (p<<med>0.01) and ADMA (p<0.05), whereas negatively to EPC number (p<0.05).
Conclusions: Plasma ADMA is elevated in RA subjects free of CV disease or risk factors, which has been shown for the first time. ADMA accumulation may contribute to EPC depletion via depressed NO-dependent EPC mobilization and/or survival with consequent impairment of the EPC-mediated endothelial repair, which can promote atherogenesis in RA.