Abstract
Abstract P261: Vasopressin System Components are Dysregulated in Human Preeclamptic Placenta
Hypertension (Dallas, Tex. 1979), Vol.70(suppl_1)
09/2017
DOI: 10.1161/hyp.70.suppl_1.p261
Abstract
Preeclampsia (PE) is a cardiovascular disorder of late pregnancy characterized by pregnancy-specific onset of hypertension and proteinuria. Although initiating events leading to PE development remain unclear, emerging studies suggest arginine vasopressin (AVP) signaling may contribute to PE pathogenesis, as elevated circulating copeptin (a stable biomarker of AVP secretion) levels precede the onset of human PE, and chronic infusion of AVP into wildtype mice phenocopies PE. Here, we tested the hypothesis that AVP signaling is dysregulated in PE placenta by performing
in-silico
reanalysis of a publically available gene expression dataset derived from placentas of human PE and normal pregnancies (GSE75010). Significant increases in expression [log
2
values] of
AVP
(Con: 6.96 ± 0.02, PE: 7.03 ± 0.17, p=0.005) and its receptors
AVPR1a
(Con: 5.73 ± 0.02, PE: 5.80 ± 0.02, p=0.03) and
OXTR
(Con: 6.58 ± 0.02, PE: 6.65 ± 0.02, p=0.003) were observed in PE placentas (n=80) compared to normal placentas (n=77). Preeclamptic placentas also displayed an enrichment in a hypoxic gene signature, as shown by gene set enrichment analyses (NES: 1.75, FDR q<0.001, FWER p <0.001), suggesting that these placentas exhibited increased hypoxia-related signaling. Interestingly,
AVPR1a
expression as well as
OXTR
is positively and significantly correlated with the expression of two hypoxia-inducible genes
HK2
and
DDIT4
(
AVPR1a
v
HK2
: r
2
=0.04, p=0.02,
AVPR1a
v
DDIT4
: r
2
=0.06, p=0.003,
OXTR
v
HK2
: r
2
=0.05, p=0.007,
OXTR
v
DDIT4
: r
2
=0.04, p=0.008). To further elucidate the role hypoxia may play in promoting AVP signaling, HTR8/SVNeo cells (immortalized human first trimester trophoblasts) were treated with the hypoxia mimetic dimethyloxallyl glycine (DMOG). DMOG incubation did not significantly alter the expression of
AVP
and
AVPR1a
. Unexpectedly, a marked reduction in
OXTR
expression was observed upon DMOG treatment. In summary, these data suggest that 1) components of the AVP signaling pathway are aberrantly expressed in human PE placentas, 2) PE placentas exhibit a gene expression signature consistent with increased canonical hypoxia signaling, and 3) hypoxia may not be the cause of elevated placental
AVP
,
AVPR1a
, and
OXTR
expression in human PE.
Details
- Title: Subtitle
- Abstract P261: Vasopressin System Components are Dysregulated in Human Preeclamptic Placenta
- Creators
- Guorui Deng - University of IowaKatherine J Perschbacher - University of IowaJeremy A Sandgren - University of IowaNanmeng Yu - University of IowaSabrina M Scroggins - University of IowaEric J Devor - University of IowaDonna A Santillan - University of IowaKatherine N Gibson-Corley - University of IowaCurt D Sigmund - University of IowaAnne E Kwitek - University of IowaMark K Santillan - University of IowaJustin L Grobe - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.70(suppl_1)
- DOI
- 10.1161/hyp.70.suppl_1.p261
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Molecular Physiology and Biophysics; Neuroscience and Pharmacology; Obstetrics and Gynecology; The University of Iowa Institute for Vision Research; Internal Medicine
- Record Identifier
- 9984317117102771
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