Vaughan, Owen R;
Goodspeed, Andrew;
Sucharov, Carmen C;
Powell, Theresa L;
Jansson, Thomas;
(2025)
Human fetal circulating factors from pregnancies complicated by obesity upregulate genes associated with pathological hypertrophy in neonatal rat cardiomyocytes.
American Journal of Physiology-Heart and Circulatory Physiology
, Article ajpheart.00375.2025. 10.1152/ajpheart.00375.2025.
(In press).
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Abstract
Obesity in pregnant women increases offspring cardiovascular risk and causes fetal cardiac dysfunction. The underpinning mechanisms remain unclear. We hypothesised that circulating factors in serum from fetuses of women with obesity induce pathological cardiomyocyte hypertrophy. Pregnant women with obesity or healthy weight were recruited at term and provided umbilical cord serum and placentas, which were used for isolation of primary trophoblast cells. Primary cardiomyocytes were isolated from neonatal rats. Compared to cord serum from healthy weight women, cord serum from women with obesity upregulated cardiomyocyte mRNA expression of atrial natriuretic factor (Anf) and brain natriuretic peptide (Bnp) and increased the ratio of beta- to alpha-myosin heavy chain expression (Myh7:Myh6), when it was supplemented into the culture medium. This effect was prevented by treating the cord serum with heat-freeze cycling and DNase or RNase digestion. Separately, conditioned medium from trophoblast cells from women with obesity increased cardiomyocyte Anf expression without altering Bnp or Myh7:Myh6. MicroRNAs miR-142 and miR-17, which are associated with cardiac function, were increased in abundance in extracellular vesicles isolated from cord serum from women with obesity. However, miR-142-3p, miR-142-5p and miR-17-5p did not increase Anf, Bnp or Myh7:Myh6 expression when they were transfected into cardiomyocytes. Neither cord serum nor the upregulated microRNAs from women with obesity altered cardiomyocyte size. The results show that human fetal circulating and placenta-derived factors induce gene expression hallmarks of pathological hypertrophy in cardiomyocytes and may mediate cardiac dysfunction in children of women with obesity.
| Type: | Article |
|---|---|
| Title: | Human fetal circulating factors from pregnancies complicated by obesity upregulate genes associated with pathological hypertrophy in neonatal rat cardiomyocytes |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1152/ajpheart.00375.2025 |
| Publisher version: | https://doi.org/10.1152/ajpheart.00375.2025 |
| Language: | English |
| Additional information: | Copyright © 2025 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0. Published by the American Physiological Society. |
| Keywords: | cardiomyopathy, hypertrophic, diabetes, gestational, exosomes, fetal organ maturity, metabolic syndrome |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217852 |
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