Medical College of Wisconsin
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Angiotensin II-induced cardiovascular load regulates cardiac remodeling and related gene expression in late-gestation fetal sheep. Pediatr Res 2014 Jun;75(6):689-696

Date

03/13/2014

Pubmed ID

24614802

Pubmed Central ID

PMC4251591

DOI

10.1038/pr.2014.37

Scopus ID

2-s2.0-84900872345   8 Citations

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Author List

Norris AW, Bahr TM, Scholz TD, Peterson ES, Volk KA, Segar JL

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Animals
Cardiovascular Physiological Phenomena
Cell Proliferation
Female
Fetus
Gene Expression Regulation, Developmental
Immunoblotting
Losartan
Microarray Analysis
Myocytes, Cardiac
Pregnancy
Sheep
Ventricular Remodeling
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0