Renin-angiotensin system transgenic mouse model recapitulates pathophysiology similar to human preeclampsia with renal injury that may be mediated through VEGF.
Am J Physiol Renal Physiol
; 312(3): F445-F455, 2017 03 01.
Article
en En
| MEDLINE
| ID: mdl-27927648
ABSTRACT
Using a transgenic cross, we evaluated features of preeclampsia, renal injury and the sFlt1/VEGF changes. Transgenic hAGT and hREN, or wild-type (WT) C57Bl/6 mice were cross-bred female hAGT × male hREN for preeclampsia (PRE) model and female WT × male WT for pregnant controls (WTP). Samples were collected for plasma VEGF, sFlt1, and urine albumin. Blood pressures (BP) were monitored by telemetry. Vascular reactivity was investigated by wire myography. Kidneys and placenta were immunostained for sFlt1 and VEGF. Eleven PRE and 9 WTP mice were compared. PRE more frequently demonstrated albuminuria, glomerular endotheliosis (80% vs. 11%; P = 0.02), and placental necrosis (60% vs. 0%; P < 0.01). PRE group demonstrated declining BPs with advancing gestation. Plasma sFlt1 increased across pregnancy in PRE; VEGF did not vary. IHC demonstrated the presence of sFlt1 in glomeruli, lymphatics, and collecting tubules of PRE kidneys, suggesting excretion. VEGF immunostaining was increased specifically in the glomeruli of PRE kidneys. Placenta in PRE showed marked immunostaining for sFlt1. We conclude that this transgenic model of preeclampsia recapitulates human preeclamptic state with high fidelity, and that, vascular adaptation to pregnancy is suggested by declining BPs and reduced vascular response to PE and increased response to acetylcholine. Placental damage with resultant increased release of sFlt1, proteinuria, deficient spiral artery remodeling, and glomerular endotheliosis were observed in this model of PRE. Increased VEGF binding to glomerular endothelial cells in this model of PRE is similar to human PRE and leads us to hypothesize that renal injury in preeclampsia may be mediated through local VEGF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Placenta
/
Preeclampsia
/
Sistema Renina-Angiotensina
/
Presión Sanguínea
/
Angiotensinógeno
/
Renina
/
Células Endoteliales
/
Factor A de Crecimiento Endotelial Vascular
/
Enfermedades Renales
/
Glomérulos Renales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Asunto de la revista:
FISIOLOGIA
/
NEFROLOGIA
Año:
2017
Tipo del documento:
Article