Objective To investigate the effects of neuropeptide Y (NPY) on angiogenesis and endothelial function in preeclampsia (PE). Methods In animal experiments, a rat model of PE was established by subcutaneous injection of N-nitro-L-arginine methyl ester (L-NAME). The successfully modeled PE rats were randomly divided into 5 groups (n=12): rPE group, rNC-sh group, rNPY-sh group, rNC-oe group and rNPY-oe group, and 12 normal pregnant rats were used as the control group (rCon group). Normal saline was injected into the tail vein of the rats in the rCon group and rPE group, and NC-sh, NPY-sh, NC-oe and NPY-oe lentiviruses were injected into the tail vein of the rats in the rNC-sh group, rNPY-sh group, rNC-oe group and rNPY-oe group, respectively. On the 21st day of pregnancy, systolic blood pressure (SBP), 24-hour urine protein and serum concentrations of angiotensin II (Ang II), endothelin-1 (ET-1), and nitric oxide (NO) were measured in rats. The placental morphology was observed by hematoxylin-eosin (HE) staining. In cell experiments, the human chorionic trophoblast cell lines (HTR-8/SVneo) were divided into cCon group (not transfected), cH/R group (not transfected), cH/R+NC-sh group (transfected with NPY-sh), cH/R+NPY-sh group (transfected with NPY-sh), cH/R+NC-oe group (transfected with NPY-oe) and cH/R+NPY-oe group (transfected with NPY-oe). Cells in cCon group were cultured for 48 h, and cells in other groups were treated with H/R for 48 hours. Cell proliferation was detected by CCK-8 method and EdU staining, cell apoptosis was detected by TUNEL staining, and cell migration motility was detected by Transwell. RT-qPCR or Western blot was used to detect the expression of NPY, Y1 receptor (Y1R), Y2 receptor (Y2R), soluble fms-like tyrosine kinase 1 (sFlt1), vascular endothelial growth factor (VEGF), and placental growth factor (PIGF) in placenta and cells. Results In animal experiments, after tail vein injection of NPY-sh into PE rats, the mRNA and protein levels of NPY, Y1R, and Y2R were decreased; SBP and 24-hour urinary protein were reduced; placental sinusoids were increased, inflammatory cell infiltration was decreased; the protein level of sFlt1 in the placenta was increased, while the protein levels of VEGF and PIGF were decreased; the serum levels of Ang II and ET-1 were decreased, and the level of NO was increased. However, after tail vein injection of NPY-oe into PE rats, the changes in various indicators were completely opposite to those in rats injected with NPY-sh. In cell experiments, among the cells treated with H/R, the mRNA and protein levels of NPY, Y1R, and Y2R, the TUNEL-positive rate, and the protein levels of VEGF and PIGF were all decreased in cells transfected with NPY-sh, while the relative cell viability, EdU-positive rate, number of invasive cells, and sFlt1 protein level were all increased. However, transfection with NPY-oe group induced exactly the opposite changes in all measured indicators compared to the NPY-sh group. Conclusion The abnormal expression of NPY affects angiogenesis and endothelial function in PE. NPY may induce angiogenesis through Y2R, stimulate vasoconstriction and aggravate endothelial function damage through Y1R.
Key words
preeclampsia /
neuropeptide Y /
Y1 receptor /
Y2 receptor /
angiogenesis /
endothelial function
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