RESUMO
BACKGROUND: Preeclampsia and gestational hypertension can cause vascular function impairment in offspring. In our previous work, we described the protein expression profiles of umbilical artery tissues from patients with preeclampsia. METHODS: To gain insights into the mechanisms of vascular dysfunction in adult rats born to preeclamptic dams, we analyzed thoracic aorta tissues by using iTRAQ isobaric tags and 2D nano LC-MS/MS. RESULTS: By using the iTRAQ method, we analyzed 1825 proteins, of which 106 showed significantly different expression in the thoracic aortic. Ingenuity pathway analysis (IPA) showed that the majority of differentially expressed proteins (DEPs) were associated with cardiovascular function. Further analysis indicated that glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by miR-423-5p and activated by TP53, had the strongest effect on cardiovascular function. The expression of G6PD was upregulated in thoracic aorta tissues, as confirmed by Western blotting. The expression of two other vascular function-related proteins, cysteine- and glycine-rich protein 2 (CSRP2) and tubulin alpha-4 A (TUBA4A), was upregulated, as demonstrated by mass spectrometry (MS). CONCLUSIONS: Although the results require further functional validation, these data provide novel findings related to vascular function impairment in the adult offspring of preeclamptic mothers.
RESUMO
Background and aim: Although studies have associated elevated prenatal obesity with increased risk of various diseases in offspring, little is known regarding the immune system. The aim of this study was to evaluate the relationship between prenatal obesity and levels of cytokines in umbilical cord blood and development of allergic disease during the first 10 years of life in an offspring. Methods: A cohort of term infants born at the ShaoXing Women and Children Hospitals in China in 2011 was enrolled in this study. Flow cytometry was performed to measure levels of various cord blood cytokines, namely IL1ß, IL2, IL10, IL6, IL8, IL17, IL12, TNF-α and IFN-γ. Next, logistic regression was used to explore the association of prenatal BMI with the development of allergic disease. The relationship between levels of each cord blood cytokine with prenatal BMI, and allergic disease development was tested using linear and logistic regression analyses, respectively. Results: After 10 years of follow-up, higher prenatal BMI was significantly associated with development of allergic disease in children (HR = 2.45, 95% CI:1.08-5.57, P = 0.033). We also adjusted for maternal age, education and infant gender, and found that prenatal BMI was significantly associated with higher levels of IL12 (P = 0.023) and IL1ß (P = 0.049) in cord blood. Moreover, we adjusted for maternal age, education, allergic dermatitis, gestation age and infant gender, and found that increase in each unit (1.26 pg/ml) in IL17 was associated with a 55.5% higher risk of allergic disease in 10-year-old children (HR = 1.55, 95%Cl: 0.99-2.45, P = 0.056). Meanwhile, after adjusting for maternal age, education level, gestation age, prenatal BMI, gestational weight gain, infant gender and birthweight, we found that for every unit increase in IL10, IL6 and IL1ß, the risk of overweight/obesity in children after 10-year follow-up increased by 18.7% (HR = 1.19, 95%Cl: 1.01-1.40, P = 0.042), 13.9% (HR = 1.14, 95%Cl: 1.02-1.27, P = 0.021) and 41.3% (HR = 1.41, 95%Cl: 1.02-1.95, P = 0.036), respectively. Conclusions: Prenatal obesity was positively correlated with allergic diseases in offspring. Cord blood cytokine may play mediating roles in the associations of prenatal obesity with offspring allergic diseases.