TOP SCORING SCIENTIFIC ABSTRACT SESSION S-1. Association of coronary artery vitamin D receptor expression and Systemic Risk Factors for Coronary Artery Atherosclerosis

S-1. Association of coronary artery vitamin D receptor expression and Systemic Risk Factors for Coronary Artery Atherosclerosis Ran Xie, M.D., Ph.D.1, Xuezhi Jiang, MD1, David M. O’Sullivan, PhD1, Peter F. Schnatz, D.O.1,2. 1ObGyn & Internal Medicine, The Reading Hospital and Medical Center, Reading, PA; 2ObGyn & Internal Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA Objective: The results of previous studies have determined that an inverse correlation exists between coronary artery vitamin D receptor (VDR) expression and the degree of coronary artery atherosclerosis (CAA). It is not clear whether VDRs decrease after CAA develops, suggesting a local response to CAA, or whether systemic factors lead to decreased VDRs suggesting the VDR quantity may be an indicator of future CAA. The current study analyzes the association between coronary VDR expression (as an H-score) and systemic CAA risk factors. Design: Premenopausal cynomolgus monkeys (n=39) were fed atherogenic diets containing the equivalent of 1,000 IU/day of 25OHD3. After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 post-menopausal months, CAA was measured in the left circumflex artery (LCX) and left anterior descending artery (LAD). VDR expression was quantified in the LAD and monocyte chemotactic protein-1 (MCP-1), an inflammatory marker, was assessed. Concurrently, plasma 25OHD3 and lipid profiles were assessed. Correlations were analyzed with Spearman’s rho (R) and differences between groups were evaluated with Kruskal-Wallis and post hoc Games-Howell tests using alpha=0.05. Results: In postmenopausal monkeys receiving an atherogenic diet, MCP-1 was significantly elevated compared with monkeys at baseline (p<0.001) and in those at the start of menopause (oophorectomy) (p<0.001). Coronary VDR expression was inversely correlated with MCP-1 (R=-0.328, p=0.042). When VDR expression was grouped by tertile, as VDR quantity increased, there was a corresponding decrease in MCP-1 (p=0.039). Additionally, the change of postmenopausal MCP-1 (from baseline to necropsy) was significantly reduced in the group with higher, compared to < the median, VDR H-Score quantification (p=0.038). The combination of plasma 25OHD3 and TPC:HDL-C were subsequently broken into low-, moderate-, and high-risk groups; as the risk increased, VDR quantity decreased (p=0.04), see figure 1. Conclusion: Coronary artery VDR expression was inversely correlated with systemic CAA risk factors. These findings suggest that an increased level and/or severity of systemic CAA risk factors may lead to a loss of coronary artery VDR, either with or after CAA progression. This, in turn, would support the translational hypothesis that women who would most benefit from 25OHD3 supplementation would be those in the preto peri-menopausal years, before they develop significant CAA and hence lose substantial coronary artery VDR expression.