Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Vitamin D has an important role in the immune system, and has been linked to inflammation, rheumatoid arthritis (RA) and coronary artery disease (CAD)[1, 2]. However, the exact mechanisms how vitamin D is involved in these processes are still unclear. Therefore, the aim of this study was to compare the expression of vitamin D receptor (VDR) associated genes in the aortic adventitia of CAD patients with and without RA.
Methods: RNA was isolated, and Affymetrix microarray was used to determine the gene expression profile in specimens from the ascending aorta in 8 patients with CAD and 8 patients with CAD and RA from the Feiring Heart Biopsy Study. Partek Genomics Suite software was used to identify differentially expressed genes by one-way ANOVA (p<0.05; FC>1.1), and differences in expression of VDR associated genes were determined by Ingenuity Pathway Analysis.
Results: Among the 15586 transcripts that were identified, pathway analysis determined two genes within the VDR signaling pathway, Growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) (p=0.006; FC=1.474) and Nuclear Receptor Corepressor 1 (NCOR1) (p=0.005; FC=1,210), that where both up-regulated in RA patients.
Conclusion: GADD45A induces cell cycle arrest, DNA repair and apoptosis in response to various environmental stresses , and NCOR1 has an important role as a gene-specific integrator of positive and negative signals that control inflammation . In theory, the accelerated atherosclerosis in RA might be related to the up-regulation of GADD45A and NCOR1 through the VDR signaling pathway. 1. Urruticoechea-Arana, A., et al., Vitamin D deficiency in chronic inflammatory rheumatic diseases: results of the cardiovascular in rheumatology [CARMA] study. Arthritis Res Ther, 2015. 17: p. 211.
2. Norman, P.E. and J.T. Powell, Vitamin D and cardiovascular disease. Circ Res, 2014. 114(2): p. 379-93.
3. Rosemary Siafakas, A. and D.R. Richardson, Growth arrest and DNA damage-45 alpha (GADD45alpha). Int J Biochem Cell Biol, 2009. 41(5): p. 986-9.
4. Glass, C.K. and K. Saijo, Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat Rev Immunol, 2010. 10(5): p. 365-76.
To cite this abstract in AMA style:Oma I, Holm S, Andersen JK, Olstad OK, Fostad IG, Lyberg T, Almdahl SM, Molberg Ø, Hollan I. Expression of Vitamin D Receptor Associated Genes in the Aorta of Coronary Artery Disease Patients with and without Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/expression-of-vitamin-d-receptor-associated-genes-in-the-aorta-of-coronary-artery-disease-patients-with-and-without-rheumatoid-arthritis/. Accessed July 7, 2020.
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