Angiotensin II-induced cardiovascular load regulates cardiac remodeling and related gene expression in late-gestation fetal sheep

Andrew W Norris; Timothy M Bahr; Thomas D Scholz; Emily S Peterson; Ken A Volk; Jeffrey L Segar

doi:10.1038/pr.2014.37

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Angiotensin II-induced cardiovascular load regulates cardiac remodeling and related gene expression in late-gestation fetal sheep

Journal article

Open access

Peer reviewed

Angiotensin II-induced cardiovascular load regulates cardiac remodeling and related gene expression in late-gestation fetal sheep

Andrew W Norris, Timothy M Bahr, Thomas D Scholz, Emily S Peterson, Ken A Volk and Jeffrey L Segar

Pediatric research, Vol.75(6), pp.689-696

06/2014

DOI: 10.1038/pr.2014.37

PMCID: PMC4251591

PMID: 24614802

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Abstract

Angiotensin II (ANG II) stimulates fetal heart growth, although little is known regarding changes in cardiomyocyte endowment or the molecular pathways mediating the response. We measured cardiomyocyte proliferation and morphology in ANG II-treated fetal sheep and assessed transcriptional pathway responses in ANG II and losartan (an ANG II type 1 receptor antagonist) treated fetuses. In twin-gestation pregnant sheep, one fetus received ANG II (50 μg/kg/min i.v.) or losartan (20 mg/kg/d i.v.) for 7 d; noninstrumented twins served as controls. ANG II produced increases in heart mass, cardiomyocyte area (left ventricle (LV) and right ventricle mononucleated and LV binucleated cells), and the percentage of Ki-67-positive mononucleated cells in the LV (all P < 0.05). ANG II and losartan produced generally opposing changes in gene expression, affecting an estimated 55% of the represented transcriptome. The most prominent significantly affected biological pathways included those involved in cytoskeletal remodeling and cell cycle activity. ANG II produces an increase in fetal cardiac mass via cardiomyocyte hypertrophy and likely hyperplasia, involving transcriptional responses in cytoskeletal remodeling and cell cycle pathways.

Cardiovascular Physiological Phenomena

Angiotensin II - pharmacology

Cell Proliferation

Angiotensin II - metabolism

Gene Expression Regulation, Developmental - drug effects

Losartan - pharmacology

Immunoblotting

Ventricular Remodeling - physiology

Angiotensin II Type 1 Receptor Blockers - pharmacology

Fetus - physiology

Pregnancy

Animals

Myocytes, Cardiac - drug effects

Analysis of Variance

Microarray Analysis

Myocytes, Cardiac - physiology

Female

Sheep

Ventricular Remodeling - drug effects

Gene Expression Regulation, Developmental - physiology

Details

Title: Subtitle: Angiotensin II-induced cardiovascular load regulates cardiac remodeling and related gene expression in late-gestation fetal sheep
Creators: Andrew W Norris - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Timothy M Bahr - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Thomas D Scholz - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Emily S Peterson - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Ken A Volk - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Jeffrey L Segar - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Pediatric research, Vol.75(6), pp.689-696
Publisher: United States
DOI: 10.1038/pr.2014.37
PMID: 24614802
PMCID: PMC4251591
ISSN: 0031-3998
eISSN: 1530-0447
Grant note: R01 HL080657 / NHLBI NIH HHS R01 DK097820 / NIDDK NIH HHS DK097820 / NIDDK NIH HHS HL080657 / NHLBI NIH HHS
Language: English
Date published: 06/2014
Academic Unit: Endocrinology and Diabetes; Cardiology; Stead Family Department of Pediatrics; Child and Community Health; Biochemistry and Molecular Biology
Record Identifier: 9984025262602771

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