Open AccessLow birth weight activates the renin–angiotensin system, but limits cardiac angiogenesis in early postnatal life
Author(s) -
Wang Kimberley C. W.,
Brooks Doug A.,
SummersPearce Brooke,
Bobrovskaya Larisa,
Tosh Darran N.,
Duffield Jaime A.,
Botting Kimberley J.,
Zhang Song,
Caroline McMillen I.,
Morrison Janna L.
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12270
Subject(s) - cardiac fibrosis , endocrinology , medicine , angiotensin ii , dna methylation , low birth weight , renin–angiotensin system , biology , fibrosis , receptor , gene expression , pregnancy , biochemistry , blood pressure , genetics , gene
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 ACE 2 mRNA , decreased ANGII receptor type 1 ( AT 1 R) protein, and acetylation of histone H3K9 of the AT 1 R promoter but no changes in AT 1 R mRNA expression and AT 1 R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC 5 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.