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

Abstract

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 D₃. 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 25OHD₃ 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.

摘要

目的：本研究的目的是分析冠状动脉维生素D受体（VDR）的表达与系统性冠状动脉粥样硬化（CAA）危险因素的关系。

方法：雌性食蟹猴（n=39）每天摄入致动脉粥样硬化饮食, 包含相当于女性1000 IU/天的维生素D₃。在这样摄入饮食32个月后, 每只猴子都经历了手术性绝经。绝经后32个月后, 对冠状动脉左前降支CAA和VDR的表达进行定量。测定血浆25OHD₃、血脂及血清单核细胞趋化蛋白-1（MCP-1）水平。

结果：绝经后摄入致动脉粥样硬化饮食的猴子血清MCP-1水平显著高于基线（482.2±174.2 pg/ml vs. 349.1±163.2 pg/ml; p<0.001; d=0.79）和绝经开始时（363.4±117.2 pg/ml; p<0.001; d=0.80）。冠状动脉VDR表达与MCP-1呈负相关（p=0.042）。此外, VDR高表达组绝经后MCP-1的变化（从基线到尸检）显著低于中等表达组（p=0.038）。随后将血浆25OHD₃和总胆固醇/高密度脂蛋白胆固醇的组合分为低危组、中危组和高危组；随着风险的增加, VDR数量减少（p=0.04）。CAA与各种致动脉粥样硬化饮食无关。

结论：冠状动脉VDR表达与CAA风险和炎症指标, 包括MCP-1, 呈负相关, 提示动脉中的全身性和局部炎症可能与动脉VDR表达降低有关。

Keywords:

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

Additional information

Funding

Funding sources for this research and article were research budgets of Wake Forest University Primate Center and The Reading Hospital and Medical Center; original study was supported by National Institutes of Health [HL079421] (J.R.K.); [P01 HL 45666] (T.B.C., J.R.K.).