Profiling of cardiovascular and cerebrovascular disease associated microRNA expression in umbilical cord blood in gestational hypertension, preeclampsia and fetal growth restriction.

BACKGROUND AND METHODS: Gene expression of 29 cardiovascular and cerebrovascular disease associated microRNAs was assessed in whole umbilical cord blood, compared between groups [47 gestational hypertension (GH), 56 preeclampsia (PE), 37 fetal growth restriction (FGR) and 44 normal pregnancies] and correlated with the severity of the disease with respect to clinical signs (mild PE vs. severe PE), delivery date (before and after 34weeks of gestation), and Doppler ultrasound parameters [pulsatility index (PI) in the umbilical artery, PI in the middle cerebral artery and the cerebroplacental ratio].

RESULTS: GH showed a down-regulation of miR-195-5p (p=0.025). The down-regulation of miR-26a-5p (p=0.031, p=0.05), miR-145-5p (p=0.042, p=0.015), and miR-574-3p (p=0.002, p=0.022) was observed in severe PE pregnancies requiring termination before 34weeks of gestation. Severe PE occurring regardless of the delivery date was associated with downregulation of miR-195-5p (p=0.01), miR-199a-5p (p=0.048), and miR-221-3p (p=0.028). On the other hand, mild PE showed upregulation of miR-92a-3p (p=0.044). The centralization of fetal circulation tended to higher levels of miR-1-3p (ρ=-0.302, p=0.045) and miR-133a-3p (ρ=-0.348, p=0.020) in PE pregnancies. FGR pregnancies with abnormal values of flow rate in the umbilical artery (miR-221-3p: ρ=-0.390, p=0.017) and the middle cerebral artery (miR-143-3p: ρ=0.350, p=0.036) demonstrated down-regulation of relevant microRNAs.

CONCLUSION: Epigenetic changes induced by pregnancy-related complications in umbilical cord blood may appear as a result of dysfunctional placenta and impaired maternal cardiovascular function (hidden cardiovascular and cerebrovascular diseases) and may cause later onset of cardiovascular and cerebrovascular diseases in offspring.