Session Type: Abstract Submissions (ACR)
Background/Purpose: The cardiovascular comorbidity seen in early treatment naive rheumatoid arthritis (RA) can be considered as an aspect of ´´accelerated aging“.
Methods: We investigated cell migration and proliferation of human cells in vitro in a so-called wound healing assay, using telomerase-immortalized mesenchymal stem cells (hTERT-MSC)1. Confluent monolayers of hTERT-MSC were mechanically “wounded” creating a fixed size scratch and then allowed to “heal” in the presence of culture medium containing 5% serum from RA-patients (n=30) or healthy subjects (n=25) for 3 days. We examine the effect of serum from RA-patients and controls on hTERT-M and to correlate these in vitro measures to standardized measures of cardiopulmonary parameters assessing global longitudinal systolic strain (GLS) by speckle tracking echocardiography2, coronary calcium score (Agaston score) by coronary computer tomography (CT COR), diffusing capacity of the lungs for carbon monoxide (DLCO), LDL, C-reactive protein (CRP), fasting Insulin (fIns) levels and whole body fat percent by whole body DXA-scan. The assay was performed on serum from 30 treatment-naive RA patients (mean age 56 yr; range 27-73) and 24 healthy controls (age 44 yr; range 24-64).RA patients and controls were free of medication at the time of serum sampling (the RA patients received methotrexate treatment at year one). Disease activity was scored by the use of the Danish national DANBIO registry using standard assessments. CCP titers, LDL and fIns were evaluated by standardized techniques before treatment was initiated.
Results: We found ´´accelerated aging“ measured as decreased wound healing in vitro by mean 53% (range 20-100%) in RA patients compared to healthy controls (p<0.0001). One year of national guideline DMARD treatment improved the ´´in vitro decreased wound healing“ to mean 60% although not significant (p=0.068). We found ´´decreased wound healing in vitro“ to be associated with increased LDL levels (p=0.02; r=0.43) in univariate analysis (no association to GLS, Agaston calcium score, DLCO (mmol/min/kPa/L), total fat %, fIns and CRP (p-values in the range 0.31-0.79). We also found a significant difference in GLS in patients with high values of anti-CCP (titers ≥ 340) compared to patients with normal titers and anti-CCP titers <340 (p=0.04). Similarly DLCO was found decreased in patients with increased anti-CCP titers. Anti-CCP larger than 7 and below 340 p=0.02 (DLCO mean 88%) and if anti>340 p=0.004 (DLCO mean 82%) in anti-CCP negative patients mean DLCO% 102%.
Conclusion: We observed a significant decreased ´´wound healing in vitro “ using hTERT-MSC assay in early RA. The ´´decreased in vitro wound healing“ was significantly associated with increased LDL. Further we found a significant association between increased anti-CCP titers and initial increased cardiac function and decreased pulmonary function.
References: 1 Demirovic, D. and Rattan, S.I.S. Biogerontology, 12: 437-444, 2011
2 Løgstrup BB et al: In Press. American Journal of Cardiovascular Disease.
B. B. Løgstrup,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/accelerated-aging-in-dmard-and-treatment-naive-early-rheumatoid-arthritis-patients-measured-by-a-stem-cell-assay-is-associated-with-increased-ldl-and-is-linked-to-impaired-cardiopulmonary-function/