110. Preeclamptic plasma affects gene expression in human endothelial cells and vascular smooth muscle cells

Abstract

Introduction One of the main preeclampsia features is maternal vascular dysfunction. In rat experimental preeclampsia we have previously shown that this includes changes in vascular gene expression (Lip et al. Sci. Rep. 7, 14807(2017)). Objective We tested whether vascular gene expression in experimental preeclampsia can be induced by incubation of human endothelial and vascular smooth muscle cells with preeclamptic plasma in vitro. Methods Human umbilical vein endothelial cells (HUVEC) and human aortic vascular smooth muscle cells (VSMC) were incubated with 15% plasma from early-onset preeclamptic (n = 5), healthy pregnant (n = 5) or non-pregnant women (n = 5) for 24 h. RNA was isolated from the cells and RT-RT-PCR was performed to determine gene expression. We measured top dysregulated vascular genes in experimental preeclampsia (KCNA6, ESM1 for HUVEC and TTN, ACTC1, CHRNA3 for VSMC). Additionally, we measured expression of genes which might be altered in the vasculature during preeclampsia (NOS3, EDN1, PTGIS, CXCL8 for HUVEC and MYL6, MYL9, ACTG2 and ACTA2 for VSMC). Results Stimulation of HUVEC with preeclamptic plasma induced upregulation of KCNA6, ESM1 and CXCL8 compared to healthy pregnant plasma, while expression of NOS3, EDN1 and PTGIS was not affected. Stimulation of VSMC with preeclamptic plasma induced upregulation of ACTC1 compared to healthy pregnant plasma and upregulation of CHRNA3, MYL6, ACTG2 and ACTA2 compared to plasma from non-pregnant women, while expression of TTN and MYL9 was not affected. Discussion Using gene expression array data from the vasculature of a preeclamptic rat model, we selected potential targets to be upregulated in endothelial cells and vascular smooth muscle cells by preeclamptic plasma. The upregulation of genes by preeclamptic plasma may suggest that these gene are upregulated in vivo in preeclamptic women inducing vascular dysfunction in this condition. We next aim to determine which factors in the circulation of preeclamptic women induce these effects.