- Title
- The soluble (pro)renin receptor promotes a preeclampsia-like phenotype both in vitro and in vivo
- Creator
- Schofield, Lachlan G.; Delforce, Sarah J.; Pryor, Jennifer C.; Endacott, Saije K.; Lumbers, Eugenie R.; Marshall, Sarah A.; Pringle, Kirsty G.
- Relation
- ARC.FT150100179 http://purl.org/au-research/grants/arc/FT150100179
- Relation
- Hypertension Research Vol. 47, p. 1627-1641
- Publisher Link
- http://dx.doi.org/10.1038/s41440-024-01678-8
- Publisher
- Nature
- Resource Type
- journal article
- Date
- 2024
- Description
- Preeclampsia is classified as new-onset hypertension coupled with gross endothelial dysfunction. Placental (pro)renin receptor ((P)RR) and plasma soluble (P)RR (s(P)RR) are elevated in patients with preeclampsia. Thus, we aimed to interrogate the role (P)RR may play in the pathogenesis of preeclampsia. Human uterine microvascular endothelial cells (HUtMECs, n = 4) were cultured with either; vehicle (PBS), 25–100 nM recombinant s(P)RR, or 10 ng/ml TNF-a (positive control) for 24 h. Conditioned media and cells were assessed for endothelial dysfunction markers via qPCR, ELISA, and immunoblot. Angiogenic capacity was assessed through tube formation and adhesion assays. Additionally, pregnant rats were injected with an adenovirus overexpressing s(P)RR from mid-pregnancy (day 8.5), until term (n = 6–7 dams/treatment). Maternal and fetal tissues were assessed. HUtMECs treated with recombinant s(P)RR displayed increased expression of endothelial dysfunction makers including vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and endothelin-1 mRNA expression (P = 0.003, P = 0.001, P = 0.009, respectively), along with elevated endothelin-1 protein secretion (P < 0.001) compared with controls. Recombinant s(P)RR impaired angiogenic capacity decreasing the number of branches, total branch length, and mesh area (P < 0.001, P = 0.004, and P = 0.009, respectively), while also increasing vascular adhesion (P = 0.032). +ADV rats exhibited increased systolic (P = 0.001), diastolic (P = 0.010), and mean arterial pressures (P = 0.012), compared with -ADV pregnancies. Renal arteries from +ADV-treated rats had decreased sensitivity to acetylcholine-induced relaxation (P = 0.030), compared with -ADV pregnancies. Our data show that treatment with s(P)RR caused hypertension and growth restriction in vivo and caused marked endothelial dysfunction in vitro. These findings demonstrate the significant adverse actions of s(P)RR on vascular dysfunction that is characteristic of the preeclamptic phenotype.
- Subject
- soluble (pro)renin receptor; preeclampsia; endothelial dysfunction
- Identifier
- http://hdl.handle.net/1959.13/1506545
- Identifier
- uon:55901
- Identifier
- ISSN:0916-9636
- Rights
- x
- Language
- eng
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