Distinct uterine artery gene expression profiles during early gestation in the stroke-prone spontaneously hypertensive rat

Scott, K., Morgan, H. L., Delles, C. , Fisher, S., Graham, D. and McBride, M. W. (2021) Distinct uterine artery gene expression profiles during early gestation in the stroke-prone spontaneously hypertensive rat. Physiological Genomics, 53(4), pp. 160-171. (doi: 10.1152/physiolgenomics.00159.2020) (PMID:33719581)

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Abstract

During pregnancy the uterine spiral arteries undergo major vascular remodelling to ensure sufficient uteroplacental perfusion to support the fetus. In pregnancies complicated by hypertensive disorders this remodelling is deficient leading to impaired uteroplacental blood flow and poor maternal and fetal outcomes. The underlying genetic mechanisms for failed vascular remodelling are not fully understood. This study aimed to examine the early-pregnancy associated gene changes in the uterine arteries of stroke-prone spontaneously hypertensive rats (SHRSP) compared to their normotensive counterparts, Wistar-Kyoto rats (WKY). Uterine arteries from gestational day 6.5 WKY and SHRSP were processed for RNA-sequencing, along with virgin, age-matched controls for each strain. Gene expression changes were identified and biological pathways were implicated and interpretated using Ingenuity Pathway Analysis (IPA®). This study found that WKY uterine arteries from early-pregnancy exhibit a gene expression pattern that is suggestive of a pregnancy-dependent reduction in Ca2+ handling and RAAS components and an increase in ATP production. In contrast, the expression pattern of pregnant SHRSP uterine arteries was dominated by an elevated immune response and increased production of ROS and downstream effectors of the RAAS. These results suggest that in a rat model, hypertension during pregnancy impacts uterine artery gene expression patterns as early as the first week of pregnancy. The pathway changes involved may underlie or contribute to the adverse vascular remodelling and resultant placental ischaemia and systemic vascular dysfunction observed in SHRSP in late gestation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Graham, Dr Delyth and Morgan, Miss Hannah and McBride, Dr Martin and Scott, Kayley and Delles, Professor Christian and Fisher, Mr Simon
Authors: Scott, K., Morgan, H. L., Delles, C., Fisher, S., Graham, D., and McBride, M. W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Physiological Genomics
Publisher:American Physiological Society
ISSN:1094-8341
ISSN (Online):1531-2267
Published Online:15 March 2021
Copyright Holders:Copyright © 2021 American Physiological Society
First Published:First published in Physiological Genomics 53(4): 160-171
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302108BHF 4-Year PhD Studentship Award 2017Rhian TouyzBritish Heart Foundation (BHF)FS/17/63/33485CAMS - Cardiovascular Science
190394MRC Doctoral Training Grant 2011-2015Mary Beth KneafseyMedical Research Council (MRC)MR/J50032X/1Research and Innovation Services
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science