Henrik Thybo, Dechend Ralf, Müller Dominik. Introduction: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic.
Poster Presentations / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 3 (2013) 67–99
PP004. The polymorphism C677T of methylenetetrahydrofolate reductase (MTHFR), may increase risk for future higher blood pressure in women with previous hypertension in pregnancy Matos Andreia, da Silva Alda Pereira, Maia Helena, Ferreira Joana, Clode Nuno, Areias Maria José, Bicho Maria Clara, Bicho Manuel, Rebelo Irene Introduction: The MTHFR is a key enzyme in the folate cycle involved in homocysteine remethylation. The T allele of MTHFR C677T polymorphism is associated with lower activity inhibiting the DNA methylation and protecting from oxidative stress. Objectives: To evaluate the MTHFR genotype–phenotype relationship during and after pregnancy comparing hypertensive with normotensive women. Method: A sample of 380 women with 32.54 ± 6.478 years old, 181 normotensive (NT) and 199 hypertensive (HBP) being 70.3% above 34 weeks of gestation. A subgroup 63 women with history of preeclampsia were studied 3–6 years postpartum and compared with 59 controls. The MTHFR was evaluated by PCR-RFLP using DNA extracted from peripheral blood. Statistical analysis evaluated with appropriated tests. Results: The distribution of genotypes of the MTHFR was different according to blood pressure (BP), it was observed that the TT genotype had lower frequency in HBP (p < 0.001). In the subgroup CC + CT the MPO levels were higher in HBP as well as nitrites, leucocytes, neutrophils, Apo B, BMI, waist and ratio waist/hip compared with NT (p < 0.001, p = 0.04, p = 0.042, p = 0.035, p = 0.03, p = 0.022, p = 0.026, respectively). There were differences between levels of BP systolic and diastolic between women previously HBP and NT of CC + CT compared with TT carriers (p < 0.001). Conclusion: The MTHFR may modulate blood pressure (BP) and cardiovascular risk. TT genotype with increased expression of antioxidant enzymes, may be a protective factor for future hypertension and cardiovascular risk compared with women CC and CT genotypes with higher levels of circulating biomarkers of inflammation. doi:10.1016/j.preghy.2013.04.032
PP005. Vitamin D depletion aggravates hypertension in transgenic rats Bjørkholt Andersen Louise, Herse Florian, Christesen Henrik Thybo, Dechend Ralf, Müller Dominik Introduction: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. Objective: To investigate the impact of vitamin D in a transgenic rat model of angiotensin II-mediated hypertensive organ failure. Methods: In 4-week-old age-matched rats overexpressing the human renin and angiotensinogen genes, group 1 (n = 18) received vitamin D depleted chow; group 2 (n = 15) standard chow and intraperitoneal paricalcitol at 800 ng/kg thrice weekly; and group 3 (n = 15) standard chow and vehicle injections. Blood pressure (tail cuff) and 24-h albuminuria were determined once weekly. After three
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weeks, animals were sacrificed. Heart tissue was examined for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by RT-PCR. Results: The vitamin D depleted group had higher blood pressure at week 1 (mean difference 23.4 mm Hg, 95% CI 9.1–37.7) and tended to have higher blood pressure in weeks 2 and 3 (mean difference 14.3 mm Hg 95% CI 0.02–28.7 and 15.2 mm Hg 95% CI 1.5–33). The depletion group had higher heart-to-body weight ratio, and a trend towards higher ANP and BNP levels. The group receiving paricalcitol did not perform better. No differences were found between groups in mortality or proteinuria. Conclusion: Short-term vitamin D depletion aggravated hypertension and end-organ damage in a rat model of angiotensin II-induced hypertension. Short-term interventions with high-dose vitamin D analogues had no protective effect. doi:10.1016/j.preghy.2013.04.033
PP006. Gene expression profiling of first trimester placentas from pregnancies at high risk of developing preeclampsia Anderson Ulrik Dolberg, Thilaganathan Baskaran, Gram Magnus, Åkerström Bo, Hansson Stefan R. Introduction: Preeclampsia (PE) is an important cause of fetal and maternal morbidity and mortality. It is considered a two-stage disease, the first stage characterized by a defect placentation and the second stage by maternal manifestations. Details of the patho-physiology behind the transition from stage one to stage two remain unclear. Objective: Was to study first trimester placental gene expression in patients identified as high risk for PE by either Doppler ultrasound or the biochemical markers cell free fetal hemoglobin (HbF) and alpha-1-microglobulin (A1M). Methods: Placental samples were obtained from seven women at highrisk of PE as determined by Doppler ultrasound of the uterine arteries and eight women with normal uterine artery resistance who for other reasons terminated their pregnancies surgically. Maternal serum samples were analyzed for HbF and A1M. The patients were risk stratified according to two risk classifications: (I) High vs. low uterine artery resistance and (II) High HbF and A1M vs. low HbF and A1M. Total RNA from the placentas was used for whole genome microarray. The results were analyzed by bioinformatics and genes of interest confirmed with qPCR. Results: A total of 453 and 332 significantly altered genes were identified in the two study groups. Bioinformatics revealed 12 genes of interest in study group I and 7 genes of interest in study group II. Conclusions: Genes related to vascular tonus regulation and inflammatory response were identified in study group I suggesting that a lack of tonus regulation and increased inflammation might contribute to the high uterine artery resistance seen in this group. Genes related to regulation of hematopoiesis was found in group II suggesting dysfunctional hematopoiesis as a factor explaining the high levels of cell-free HbF seen. doi:10.1016/j.preghy.2013.04.034
