4.3 Article

Association between coronary artery vitamin D receptor expression and select systemic risks factors for coronary artery atherosclerosis

Journal

CLIMACTERIC
Volume 25, Issue 4, Pages 369-375

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/13697137.2021.1985992

Keywords

Vitamin D; vitamin D receptors; coronary artery atherosclerosis; menopause; coronary heart disease; inflammation

Funding

  1. National Institutes of Health [HL079421, P01 HL 45666]

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Through an experiment conducted on female cynomolgus monkeys, it was found that coronary artery VDR expression was associated with systemic coronary artery atherosclerosis risk factors, with high VDR expression correlating with lower systemic inflammation markers.
Objective The aim of this study is to analyze the association between coronary artery vitamin D receptor (VDR) expression and systemic coronary artery atherosclerosis (CAA) risk factors. Methods Female cynomolgus monkeys (n = 39) consumed atherogenic diets containing the women's equivalent of 1000 IU/day of vitamin D-3. After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, CAA and VDR expression were quantified in the left anterior descending coronary artery. Plasma 25OHD(3,) lipid profiles and serum monocyte chemotactic protein-1 (MCP-1) were measured. Results In postmenopausal monkeys receiving atherogenic diets, serum MCP-1 was significantly elevated compared with baseline (482.2 +/- 174.2 pg/ml vs. 349.1 +/- 163.2 pg/ml, respectively; p < 0.001; d = 0.79) and at the start of menopause (363.4 +/- 117.2 pg/ml; p < 0.001; d = 0.80). Coronary VDR expression was inversely correlated with serum MCP-1 (p = 0.042). Additionally, the change of postmenopausal MCP-1 (from baseline to necropsy) was significantly reduced in the group with higher, compared to below the median, VDR expression (p = 0.038). The combination of plasma 25OHD(3) and total plasma cholesterol/high-density lipoprotein cholesterol was subsequently broken into low-risk, moderate-risk and high-risk groups; as the risk increased, the VDR quantity decreased (p = 0.04). CAA was not associated with various atherogenic diets. Conclusion Coronary artery VDR expression was inversely correlated with markers of CAA risk and inflammation, including MCP-1, suggesting that systemic and perhaps local inflammation in the artery may be associated with reduced arterial VDR expression.

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