Vitamin D depletion does not affect key aspects of the preeclamptic phenotype in a transgenic rodent model for preeclampsia

作者：Andersen Louise Bjorkholt; Golic Michaela; Przybyl Lukasz; Sorensen Grith Lykke; Jorgensen Jan Stener; Fruekilde Palle; von Versen Hoeynck Frauke; Herse Florian; Hojskov Carsten Schriver; Dechend Ralf; Christesen Henrik Thybo; Haase Nadine^*

来源：Journal of the American Society of Hypertension, 2016, 10(7): 597-607.

DOI：10.1016/j.jash.2016.05.008

• Renin-angiotensin system
• transgenic rodents

Maternal vitamin D deficiency is proposed as a risk factor for preeclampsia in humans. We tested the hypothesis that vitamin D depletion aggravates and high supplementation ameliorates the preeclampsia phenotype in an established transgenic rat model of human renin-angiotensin system-mediated preeclampsia. Adult rat dams, transgenic for human angiotensinogen (hAGT) and mated with male rats transgenic for human renin (hREN), were fed either vitamin D-depleted chow (VDd) or enriched chow (VDh) 2 weeks before mating and during pregnancy. Mean blood pressure was recorded by tail-cuff, and 24-hour urine samples were collected in metabolic cages at days 6 and 18 of gestation. Rats were sacrificed at day 21 of gestation. Depleted dams (VDd) had negligible serum 25-hydroxyvitamin D2+3 levels (mean +/- SEM; 2.95 +/- 0.45 nmol/l vs. VDh 26.20 +/- 2.88 nmol/l, P = .01), but in both groups, levels of 1,25(OH)(2)D-3 remained below detection level of 25 prnol/l. Dietary vitamin D depletion did not aggravate hypertension (mean +/- SEM BP, day 20 of gestation: 151.38 +/- 5.65 mmHg VDd vs. 152.00 +/- 4.10 mmHg VDh) or proteinuria. Fetal anthropometrics were similar between the groups, whereas VDd displayed lower placental:fetal weight ratios (0.15 vs. 0.16 g/g, P = .01) and increased sFlt-1/PlGF ratio. Expression of hREN was lower in placenta of VDd dams (0.82 +/- 0.44 AU vs. 1.52 +/- 0.15 AU, P = .04). Expression of key vitamin D metabolizing enzymes was unchanged. Dietary vitamin D intervention did not alter key aspects of the preeclampsia phenotype using the transgenic rodent model of human renin-angiotensin system mediated preeclampsia, plausibly due to altered vitamin D metabolism or excretion in the transgenic rats.

• 出版日期2016-7