Effect of oxygen on the expression of renin–angiotensin system components in a human trophoblast cell line. (January 2016)

• Record Type: Journal Article
• Authors: Delforce, Sarah J.; Wang, Yu; Van-Aalst, Meg E.; Corbisier de Meaultsart, Celine; Morris, Brian J.; Broughton-Pipkin, Fiona; Roberts, Claire T.; Lumbers, Eugenie R.; Pringle, Kirsty G.
• Is Part Of: Placenta. Volume 37(2016:Jan.)
• Page Start: 1
• Page End: 6
• Publication Date: 2016-01
• Subjects: Renin–angiotensin system -- Pregnancy -- Placenta -- Hypoxia -- Gene expression; ACE angiotensin-converting enzyme -- ACE1 angiotensin-converting enzyme 1 -- ACE2 angiotensin-converting enzyme 2 -- AGT angiotensinogen -- AT1R angiotensin II type 1 receptor -- AGTR1 mRNA angiotensin II type 1 receptor mRNA -- Ang angiotensin -- ATP6AP2 ATPase, H+ transporting, lysosomal accessory protein 2 / (pro)renin receptor -- BCA bicinchoninic acid -- EVT extravillous trophoblast -- HIFs hypoxia inducible factors -- iNOS inducible nitric oxide synthase -- RAS renin–angiotensin system -- REN mRNA (pro)renin mRNA -- VEGF vascular endothelial growth factor; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2015.11.011
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: During the first trimester, normal placental development occurs in a low oxygen environment that is known to stimulate angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Expression of the placental renin–angiotensin system (RAS) is highest in early pregnancy. While the RAS and oxygen both stimulate angiogenesis, how they interact within the placenta is unknown. We postulated that low oxygen increases expression of the proangiogenic RAS pathway and that this is associated with increased VEGF in a first trimester human trophoblast cell line (HTR-8/SVneo). HTR-8/SVneo cells were cultured in one of three oxygen tensions (1%, 5% and 20%). RAS and VEGF mRNA expression were determined by qPCR. Prorenin, angiotensin converting enzyme (ACE) and VEGF protein levels in the supernatant, as well as prorenin and ACE in cell lysates, were measured using ELISAs. Low oxygen significantly increased the expression of both angiotensin II type 1 receptor ( AGTR1 ) and VEGF (both P < 0.05). There was a positive correlation between AGTR1 and VEGF expression at low oxygen (r = 0.64, P < 0.005). Corresponding increases in VEGF protein were observed with low oxygen ( P < 0.05). Despite no change in ACE1 mRNA expression, ACE levels in the supernatant increased with low oxygen (1% and 5%, P < 0.05). Expression of other RAS components did not change. Low oxygen increased AGTR1 and VEGF expression, as well as ACE and VEGF protein levels, suggesting that the proangiogenic RAS pathway is activated. This highlights a potential role for the placental RAS in mediating the proangiogenic effects of low oxygen in placental development. Highlights: The human placenta develops in a low oxygen environment. The placental renin–angiotensin system (RAS) is highly expressed in early pregnancy. Culture in 1% O2 increased AGTR1 mRNA and ACE protein in HTR-8/SVneo cells. The latter was associated with increased VEGF mRNA and VEGF protein. Stimulation of the placental RAS by low oxygen may be proliferative and angiogenic.