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
03/13/2014Pubmed ID
24614802Pubmed Central ID
PMC4251591DOI
10.1038/pr.2014.37Scopus ID
2-s2.0-84900872345 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
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 JLAuthor
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAngiotensin 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