Back to Search
Start Over
Renin-angiotensin system transgenic mouse model recapitulates pathophysiology similar to human preeclampsia with renal injury that may be mediated through VEGF.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2017 Mar 01; Vol. 312 (3), pp. F445-F455. Date of Electronic Publication: 2016 Dec 07. - Publication Year :
- 2017
-
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.<br /> (Copyright © 2017 the American Physiological Society.)
- Subjects :
- Albuminuria genetics
Albuminuria metabolism
Albuminuria physiopathology
Angiotensinogen genetics
Animals
Disease Models, Animal
Endothelial Cells pathology
Female
Genetic Predisposition to Disease
Gestational Age
Humans
Kidney Diseases genetics
Kidney Diseases pathology
Kidney Diseases physiopathology
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
Pre-Eclampsia genetics
Pre-Eclampsia pathology
Pre-Eclampsia physiopathology
Pregnancy
Renin genetics
Signal Transduction
Vascular Endothelial Growth Factor A blood
Vascular Endothelial Growth Factor Receptor-1 blood
Vascular Remodeling
Vasoconstriction
Vasodilation
Angiotensinogen metabolism
Blood Pressure
Endothelial Cells metabolism
Kidney Diseases metabolism
Kidney Glomerulus blood supply
Placenta blood supply
Pre-Eclampsia metabolism
Renin metabolism
Renin-Angiotensin System
Vascular Endothelial Growth Factor A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 312
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 27927648
- Full Text :
- https://doi.org/10.1152/ajprenal.00108.2016