Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of preeclampsia and other hypertensive disorders of pregnancy remains poorly-defined despite the substantial burden of maternal and neonatal morbidity associated with these conditions. In particular, the role of genetic variants as determinants of disease susceptibility remains unknown. Storkhead-box protein 1 (STOX1) was first identified as a preeclampsia risk gene through family-based genetic linkage studies in which loss-of-function variants were proposed to underlie increased preeclampsia susceptibility. We generated a genetic Stox1 loss-of-function mouse model (Stox1 KO), to evaluate whether STOX1 regulates blood pressure in pregnancy. Pregnant Stox1 KO mice developed gestational hypertension evidenced by a significant increase in blood pressure compared with wild type by E17.5. While severe renal, placental, or fetal growth abnormalities were not observed, the Stox1 KO phenotype was associated with placental vascular and extracellular matrix abnormalities. Mechanistically, we found that gestational hypertension in Stox1 KO mice resulted from activation of the uteroplacental renin-angiotensin system. We confirmed this mechanism by showing that treatment of pregnant Stox1 KO mice with an angiotensin II receptor blocker rescued the phenotype. Our study demonstrates the utility of genetic mouse models for uncovering links between genetic variants and effector pathways implicated in the pathogenesis of hypertensive disorders of pregnancy.
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PMID:STOX1 deficiency is associated with renin-mediated gestational hypertension and placental defects. 3330 24