Status of VEGF in preeclampsia and its effect on endoplasmic reticulum stress in placental trophoblast cells

Abstract

Status of VEGF in preeclampsia and its effect on endoplasmic reticulum stress in placental trophoblast cells Sankat Mochana,*, Manoj Kumar Dhingrab, Sunil Kumar Guptaa, Shobhit Saxenaa, Pallavi Aroraa, Vineeta Yadava, Neerja Rania, Kalpana Luthrae, Sadanand Dwivedid, Neerja Bhatlac, Renu Dhingraa,* a Department of Anatomy, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India b Department of Community Medicine, NC Medical college and hospital, Israna, Panipat, Haryana, 132107, India c Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India d Department of Biostatistics, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India e Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India A R T I C L E I N F O Article history: Received 5 January 2019 Received in revised form 18 May 2019 Accepted 11 June 2019 Available online 21 June 2019 Keywords: Preeclampsia UPR ER stress VEGF A B S T R A C T Objective: To explore the role of VEGF in attenuating endoplasmic reticulum stress in placental trophoblast cells. Study design: Study was divided into following parts: 1. Serum Analysis of GRP78 and VEGF using sandwich ELISA. 2. Expression of VEGF and GRP78 in placentae by immunohistochemistry (IHC). 3. In Vitro experiments. Status of ER stress markers (GRP78, eIF2α, XBP1, ATF6 and CHOP) was assessed at various time points (8 h, 14 h, 24 h) when trophoblast cells were treated with varying concentration(s) of VEGF and also by adding recombinant VEGF at protein (Immunofluorescence, Western blot) and transcript levels (qRT-PCR). Results: Increased GRP78 and decreased VEGF protein levels in sera and placentae of preeclamptic pregnant women and reduced expression of various ER stress markers at both transcript and protein levels was observed in trophoblast cells when they were exposed to recombinant VEGF thereby indicating positive role of VEGF in alleviating ER stress. Conclusions: Reduced expression of ER stress markers in trophoblast cells against increased VEGF highlighted a new window to explore prospective drugs that can be designed to modulate the activities of various ER stress sensors in order to alleviate ER stress in pregnant women with preeclampsia.