Abstract 12193: Phosphorylated Venous Endothelial Nitric Oxide Synthase is Elevated in Rheumatoid Arthritis Subjects With High Disease Activity
Introduction: Endothelial dysfunction is present in arthritis animal models and rheumatoid arthritis (RA), a population known to develop premature cardiovascular disease. Previous studies indicate inflammation modulates phosphorylation of endothelial nitric oxide synthase (eNOS) at the S1177 residue leading to endothelial impairment. The expression of eNOS in the RA vasculature has not been assessed. We investigated the hypothesis that subjects with high disease activity RA, defined by an abnormal C-reactive protein and joint count, will have reduced levels of eNOS expression as compared to low disease activity RA patients and healthy controls.
Methods: We assessed endothelial function in 10 high disease activity RA (mean age 44 years, 86% female), 14 low disease activity RA (mean age 48 years, 91% female), and 14 healthy control (HC)(mean age 43 years, 79% female) subjects by brachial artery flow mediated dilation and extracted venous endothelial cells by soft tipped J-wires from forearm catheters. RA subjects met 1987 ACR diagnostic criteria. Expression of eNOS and phosphorylated eNOS (p-eNOS) was captured by digital immunofluorescence microscopy using human umbilical vein endothelial cell (HUVEC) controls.
Results: Despite higher levels of C-reactive protein in high disease activity RA (0.27±0.05 vs 1.9±0.5 mg/dL, p=0.0001), we found the expression of p-eNOS to be significantly greater as compared to low disease activity RA and HC (0.58±0.08 vs 0.38±0.03 vs 0.36±0.08 au, respectively, p=0.02). eNOS expression was similar between high and low disease activity RA and HC (0.47±0.05 vs 0.54±0.06 vs 0.35±0.05 au, respectively, p=0.24).
Conclusion: In conclusion, we show upregulation of p-eNOS expression in high disease activity RA subjects with elevated C-reactive protein. Further studies are required to better understand the molecular mechanisms of endothelial dysfunction in RA that lead to premature cardiovascular disease.
- © 2013 by American Heart Association, Inc.