OP0282 Expression of Vitamin D Receptor Associated Genes in The Aorta of Coronary Artery Disease Patients with and without Rheumatoid Arthritis. (15th July 2016)

• Record Type: Journal Article
• Authors: Oma, I.; Andersen, J.K.; Holm, S.; Olstad, O.K.; Fostad, I.; Lyberg, T.; Almdahl, S.M.; Molberg, Ø.; Hollan, I.
• Is Part Of: Annals of the rheumatic diseases. Volume 75(2016)Supplement 2
• Page Start: 165
• Page End: 165
• Publication Date: 2016-07-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2016-eular.3143
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: 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. Objectives: To compare 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. Conclusions: We found that GADD45A and NCOR1 were upregulated in the aorta of RA patients. GADD45A induces cell cycle arrest, DNA repair and apoptosis in response to various environmental stresses [3], while NCOR1 has an important role as a gene-specific integrator of positive and negative signals that control inflammation [4]. Based on this finding, we hypothesize that the accelerated atherosclerosis in RA might be related to the up-regulation of GADD45A and NCOR1 through the VDR signaling pathway. References: Urruticoechea-Arana A, Martin-Martinez MA, Castaneda S, Piedra CA, Gonzalez-Juanatey C, Llorca J et al. Vitamin D deficiency in chronic inflammatory rheumatic diseases: results of the cardiovascular in rheumatology [CARMA] study. Arthritis Res Ther 2015;17: 211. Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res 2014;114 2: 379–93. Rosemary Siafakas A, Richardson DR. Growth arrest and DNA damage-45 alpha (GADD45alpha). The international journal of biochemistry & cell biology 2009;41 5: 986–9. Glass CK, Saijo K. Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat Rev Immunol 2010;10 5: 365–76. Disclosure of Interest: None declared