Abstract
Rheumatoid arthritis (RA) has been associated with a higher risk of developing cardiovascular (CV) diseases. It has been proposed that systemic inflammation plays a key role in premature atherosclerosis development, and is therefore crucial to determine whether systemic components from RA patients promotes endothelial cell-oxidative stress by affecting reactive oxygen species (ROS) and nitric-oxide (NO) production. The aim of this study was to evaluate whether plasma from RA patients impair NO synthesis and ROS production by using the cell-line ECV-304 as a biosensor. NO synthesis and ROS production were measured in cells incubated with plasma from 73 RA patients and 52 healthy volunteers by fluorimetry. In addition, traditional CV risk factors, inflammatory molecules and disease activity parameters were measured. Cells incubated with plasma from RA patients exhibited reduced NO synthesis and increased ROS production compared to healthy volunteers. Furthermore, the imbalance between NO synthesis and ROS generation in RA patients was not associated with traditional CV risk factors. Our data suggest that ECV-304 cells can be used as a biosensor of systemic inflammation-induced endothelial cell-oxidative stress. We propose that both NO and ROS production are potential biomarkers aimed at improving the current assessment of CV risk in RA.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology characterized by chronic inflammation of synovial membranes and articular structures of multiple joints [1,2].Biosensors 2019, 9, 32; doi:10.3390/bios9010032 www.mdpi.com/journal/biosensorsRA causes pain, impaired function of the joints, disability and concomitant comorbidities, in the cardiovascular system [2]
The waist circumference was found significantly increased in RA patients compared to healthy controls
As it has been proposed that systemic inflammation plays a role in the development of endothelial cell damage, we evaluated the capacity of plasma from RA patients to promote reactive oxygen species (ROS) production and impair NO synthesis by using
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology characterized by chronic inflammation of synovial membranes and articular structures of multiple joints [1,2].Biosensors 2019, 9, 32; doi:10.3390/bios9010032 www.mdpi.com/journal/biosensorsRA causes pain, impaired function of the joints, disability and concomitant comorbidities, in the cardiovascular system [2]. Circulating cytokines alter the function of adipose tissue, skeletal muscle, liver cells and vascular endothelium, promoting a spectrum of CV risk factors, including insulin resistance, dyslipidaemia, oxidative stress and endothelial dysfunction [10]. These traditional cardiovascular or Framingham risk factors seem to be inadequate in predicting coronary atherosclerosis in patients with RA [11]. These factors have not been differentially increased in RA patients compared to healthy controls [12,13]
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