OP0282 Expression of Vitamin D Receptor Associated Genes in The Aorta of Coronary Artery Disease Patients with and without Rheumatoid Arthritis

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 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