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Cited by 109Birth, Development, and HealthPulmonary Hypertension Research and TreatmentsPregnancy and preeclampsia studies

Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms

Rexhaj, Emrush, Bloch, Jonathan, Jayet, Pierre-Yves, Rimoldi, Stefano F., Dessen, Pierre, Mathieu, Caroline, Tolsa, Jean-François, Nicod, Pascal +2 more·2011·American Journal of Physiology-Heart and Circulatory Physiology
DOI 10.1152/ajpheart.01309.2010
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Abstract

Insults during the fetal period predispose the offspring to systemic cardiovascular disease, but little is known about the pulmonary circulation and the underlying mechanisms. Maternal undernutrition during pregnancy may represent a model to investigate underlying mechanisms, because it is associated with systemic vascular dysfunction in the offspring in animals and humans. In rats, restrictive diet during pregnancy (RDP) increases oxidative stress in the placenta. Oxygen species are known to induce epigenetic alterations and may cross the placental barrier. We hypothesized that RDP in mice induces pulmonary vascular dysfunction in the offspring that is related to an epigenetic mechanism. To test this hypothesis, we assessed pulmonary vascular function and lung DNA methylation in offspring of RDP and in control mice at the end of a 2-wk exposure to hypoxia. We found that endothelium-dependent pulmonary artery vasodilation in vitro was impaired and hypoxia-induced pulmonary hypertension and right ventricular hypertrophy in vivo were exaggerated in offspring of RDP. This pulmonary vascular dysfunction was associated with altered lung DNA methylation. Administration of the histone deacetylase inhibitors butyrate and trichostatin A to offspring of RDP normalized pulmonary DNA methylation and vascular function. Finally, administration of the nitroxide Tempol to the mother during RDP prevented vascular dysfunction and dysmethylation in the offspring. These findings demonstrate that in mice undernutrition during gestation induces pulmonary vascular dysfunction in the offspring by an epigenetic mechanism. A similar mechanism may be involved in the fetal programming of vascular dysfunction in humans.

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Crossref · 10.1152/ajpheart.01309.2010

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  • A growth-restricted fetus has fewer insulin-producing beta cells and reduced vascularization in the pancreas, and compromised structure and maturation of the brain, lungs, and liver.

    “In addition, the pancreas has fewer insulin-producing beta cells and reduced vascularization (159, 340, 473), and the structure and maturation of the brain (142), lungs (358, 359, 424, 460) and liver (209, 474) are compromised.”

    From Placental Origins of Chronic Disease (2016) · cites this paper as [460]

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Authors
Rexhaj, E., Bloch, J., Jayet, P.-Y., Rimoldi, S. F., Dessen, P., Mathieu, C., Tolsa, J.-F., Nicod, P., Scherrer, U., & Sartori, C.
Affiliations
  • Department of Internal Medicine and Botnar Center for Clinical Research, and
  • Centre Hospitalier Universitaire Vaudois (CH)
  • University of Tarapacá (CL)
Corresponding author
Sartori, Claudio
ORCID
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Published
2011-07
Volume
301
Issue
1
Pages
H247-H252
ISSN
  • 0363-6135 (ISSN-L)
  • 1522-1539
DOI
10.1152/ajpheart.01309.2010
OpenAlex
W2110834127
Cited by
109
References
32
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 11 · 2017: 8 · 2016: 13 · 2015: 13 · 2014: 7 · 2013: 15 · 2012: 12
FWCI
10.33
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
fetal programming, pulmonary vascular dysfunction, maternal undernutrition, epigenetic mechanisms, DNA methylation, hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, endothelium-dependent vasodilation, histone deacetylase inhibitors, butyrate, trichostatin A, tempol, oxidative stress, placenta, pulmonary circulation
MeSH terms
Animals, Hypoxia, Cyclic N-Oxides, Diet, Endothelium, Vascular, Female, Male, Mice, Inbred C57BL, Pregnancy, Protein Synthesis Inhibitors, Pulmonary Circulation, Pulmonary Wedge Pressure, Spin Labels, Vascular Diseases, Hypertrophy, Right Ventricular, Oxidative Stress, DNA Methylation, Caloric Restriction, Epigenesis, Genetic, Fetal Development, Mice, Histone Deacetylase Inhibitors

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