Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation
Laura M. G. Meems, Hasan Mahmud, Hendrik Buikema, Jörg Tost, Sven Michel, Janny Takens, Rikst N. Verkaik-Schakel, Inge Vreeswijk-Baudoin, Irene V. Mateo-Leach, Pim van der Harst, Torsten Plösch, Rudolf A. de Boer
American Journal of Physiology - Heart and Circulatory Physiology Published 1 December 2016 Vol. 311 no. 6, H1459-H1469 DOI: 10.1152/ajpheart.00141.2016
Laura M. G. Meems
1Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;
The effect of the vitamin D-depleted diet on 25-hydroxyvitamin D (25(OH)D) levels (A) and parathyroid hormone (PTH) levels in female F0-animals (B). **P < 0.01 vs. F0-st; ***P < 0.001 vs. F0-st rats; n = 3/group.
mRNA expression levels in F1 rats of atrial natriuretic peptide (Anp; A), vitamin D receptor (Vdr; B), renin (C), and aldosterone-1 receptor (At1r; D) in heart and kidney. mRNA expression levels are presented as fold change. *P < 0.05 vs. F1-st rats; n = 10/group.
Overview of methylation gene expression profile in kidney samples from F1-st and F1-depl rats. We only selected genes meeting the selection criteria as described above for all three methods (n = 10): Adh7 (chromosome 2); Bcl2 (chromosome 13); Capn2 (chromosome 13); Dqx1 (chromosome 4); Gyltl1b (chromosome 3); LOC499742 (chromosome 3); Otop2 (chromosome 10); Panx1 (chromosome 8); RGD1562608 (chromosome 18); and Zbtb7b (chromosome 2).
Left: quantitative (%) DNA methylation status of Panx1 in kidney, left ventricle (LV), and aorta tissue (n = 7–10 males per group). The bar diagram shows the average DNA methylation across all 8 CpG positions. Right: mRNA expression levels of Panx1 in kidney, left ventricle and aorta tissue of male F1-st (n = 10–13) and male F1-depl (n = 8–11) rats. mRNA expression levels are presented as fold change. *P < 0.05 vs. F1-st rats.
Data are means ± SE. Baseline characteristics and echocardiographic data at death of the used rats (n = 10 per group, all males). st, Standard chow; depl, vitamin D-deficient chow; BW, body weight; HW, heart weight; LVW, left ventricular weight; HR, heart rate; MV, mitral valve; A, late ventricular filling velocities; E, early ventricular filling velocities; E/A ratio, diastolic relaxation; IVSs, thickness of the interventricular septum in systole; LVIDs, left ventricular internal diameter in systole; LVPWs, thickness of the left ventricular posterior wall in systole; IVSd, thickness of the interventricular septum in diastole; LVIDd, left ventricular internal diameter in diastole; LVPWd, thickness of the left ventricular posterior wall in diastole; LVOT, left ventricular outflow tract; EF, ejection fraction; FS, fractional shortening; LV CO, left ventricular cardiac output.