Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life

Kimberley C W Wang, Doug A Brooks, Brooke Summers-Pearce, Larisa Bobrovskaya, Darran N Tosh, Jaime A Duffield, Kimberley J Botting, Song Zhang, I Caroline McMillen, Janna L Morrison

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life.

Original languageEnglish
Article numbere12270
Number of pages16
JournalPhysiological Reports
Volume3
Issue number2
DOIs
Publication statusPublished - 3 Feb 2015
Externally publishedYes

Fingerprint

Low Birth Weight Infant
Renin-Angiotensin System
Messenger RNA
Autophagy
DNA Methylation
Acetylation
Birth Weight
Histones
Fibrosis
Angiotensin I
Proteins
Chromatin Immunoprecipitation
Renin
Vascular Endothelial Growth Factor A
Real-Time Polymerase Chain Reaction
Cardiovascular Diseases
Western Blotting
Health

Cite this

Wang, K. C. W., Brooks, D. A., Summers-Pearce, B., Bobrovskaya, L., Tosh, D. N., Duffield, J. A., ... Morrison, J. L. (2015). Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life. Physiological Reports, 3(2), [e12270]. https://doi.org/10.14814/phy2.12270
Wang, Kimberley C W ; Brooks, Doug A ; Summers-Pearce, Brooke ; Bobrovskaya, Larisa ; Tosh, Darran N ; Duffield, Jaime A ; Botting, Kimberley J ; Zhang, Song ; Caroline McMillen, I ; Morrison, Janna L. / Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life. In: Physiological Reports. 2015 ; Vol. 3, No. 2.
@article{06c2dc5abf0e4736ab561f40f62fd76b,
title = "Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life",
abstract = "Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life.",
keywords = "Journal Article",
author = "Wang, {Kimberley C W} and Brooks, {Doug A} and Brooke Summers-Pearce and Larisa Bobrovskaya and Tosh, {Darran N} and Duffield, {Jaime A} and Botting, {Kimberley J} and Song Zhang and {Caroline McMillen}, I and Morrison, {Janna L}",
note = "{\circledC} 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.",
year = "2015",
month = "2",
day = "3",
doi = "10.14814/phy2.12270",
language = "English",
volume = "3",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "John Wiley & Sons",
number = "2",

}

Wang, KCW, Brooks, DA, Summers-Pearce, B, Bobrovskaya, L, Tosh, DN, Duffield, JA, Botting, KJ, Zhang, S, Caroline McMillen, I & Morrison, JL 2015, 'Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life' Physiological Reports, vol. 3, no. 2, e12270. https://doi.org/10.14814/phy2.12270

Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life. / Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L.

In: Physiological Reports, Vol. 3, No. 2, e12270, 03.02.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life

AU - Wang, Kimberley C W

AU - Brooks, Doug A

AU - Summers-Pearce, Brooke

AU - Bobrovskaya, Larisa

AU - Tosh, Darran N

AU - Duffield, Jaime A

AU - Botting, Kimberley J

AU - Zhang, Song

AU - Caroline McMillen, I

AU - Morrison, Janna L

N1 - © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

PY - 2015/2/3

Y1 - 2015/2/3

N2 - Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life.

AB - Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life.

KW - Journal Article

U2 - 10.14814/phy2.12270

DO - 10.14814/phy2.12270

M3 - Article

VL - 3

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 2

M1 - e12270

ER -