Renin-Angiotensin System Transgenic Mouse Model Recapitulates Pathophysiology Similar to Human Preeclampsia with Renal Injury that may be Mediated through VEGF.

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. 2016 Dec 07;:ajprenal.00108.2016 Authors: Denney JM, Bird CE, Gendron-Fitzpatrick A, Sampene E, Bird IM, Shah DM 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: ♀hAGT x ♂hREN for preeclampsia (PRE) model and ♀WT x ♂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...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research