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Coronary artery vitamin D receptor expression and plasma concentrations of 25-hydroxyvitamin D: their association with atherosclerosis

Schnatz, Peter F. DO, FACOG, FACP, NCMP1,2,3,4; Nudy, Matthew BS1,3; O’Sullivan, David M. PhD1; Jiang, Xuezhi MD1; Cline, J. Mark DVM, PhD5; Kaplan, Jay R. PhD5; Clarkson, Thomas B. DVM5; Appt, Susan E. DVM5

doi: 10.1097/gme.0b013e31824cfa8f
Original Articles
Editorial

Objective: The aim of this study was to analyze coronary artery vitamin D receptor (VDR) expression, the plasma concentrations of 25-hydroxyvitamin D3 (25OHD3), and their relationship with coronary artery atherosclerosis.

Methods: Premenopausal cynomolgus monkeys were fed atherogenic diets containing the equivalent of 1,000 IU/day of vitamin D3. Protein was derived from casein-lactalbumin (C/L, n = 10), soy protein isolate (soy, n = 10), or a combination (n = 19). After 32 months of consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, coronary atherosclerosis was measured in the left circumflex (LCX) artery and left anterior descending (LAD) artery. VDR expression was determined for the LAD, and 25OHD3 concentrations were assessed.

Results: Both the cross-sectional area of atherosclerotic plaques (in square millimeters) and plaque thickness (in millimeters) in the LCX as well as the LAD arteries were analyzed in these monkeys. Those with higher plasma vitamin D3 concentrations and higher VDR were compared with those with higher plasma 25OHD3 concentrations and lower VDR. Significantly smaller plaque sizes were noted with higher plasma 25OHD3 concentrations and higher VDR. For the LCX artery, there was also a significantly lower plaque size (both plaque thickness and cross-sectional area) in those with higher quantities of VDR and lower 25OHD3 concentrations versus those with lower quantities of VDR and higher plasma concentrations of 25OHD3 (P = 0.009 and P = 0.040, respectively).

Conclusions: Cynomolgus monkeys with higher quantities of VDR have significantly less atherosclerosis than do those with lower quantities of VDR and higher plasma 25OHD3 concentrations. If these findings translate to human beings, it might explain why some individuals with higher plasma concentrations of 25OHD3 have more coronary artery atherosclerosis.

From the 1Department of Obstetrics and Gynecology, The Reading Hospital and Medical Center; Reading, PA; 2Department of Internal Medicine, The Reading Hospital and Medical Center; Reading, PA; 3Department of Obstetrics and Gynecology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; 4Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; and 5Department of Pathology/Comparative Medicine, Wake Forest University, Winston-Salem, NC.

Received December 17, 2011; revised and accepted January 24, 2012.

Funding/support: The funding sources for this research and manuscript preparation were the research budgets of the Wake Forest University Primate Center and The Reading Hospital and Medical Center. In addition, the original study was supported by the following grants from the National Institutes of Health: HL079421 (J.R.K.) and PPG HL 45666 (T.B.C., J.R.K.).

Financial disclosure/conflicts of interest: Thomas B. Clarkson is a member of an advisory committee to Pfizer pharmaceuticals and has been supported by a research grant from Pfizer.

He is also the recipient of a research grant from Merck.

These data were presented in abstract form at the NAMS 22nd Annual Meeting, September 21 to 24, 2011, Washington, DC. These data and results, however, have not been published in manuscript form and have not been submitted previously to another journal.

Address correspondence to: Peter F. Schnatz, DO, FACOG, FACP, NCMP, Department of Obstetrics and Gynecology, – R1, The Reading Hospital and Medical Center, PO Box 16052, Reading, PA 19612-6052. E-mail: schnatzp@readinghospital.org

©2012The North American Menopause Society