ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012
Pulmonary artery smooth muscle cell proliferation and migration in fetal lambs acclimatized to high-altitude long-term hypoxia: role of histone acetylation.
Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 69 citations in OpenAlex.
- Arterial tracing-based technique for rapid purification of pulmonary arterial smooth muscle cells from rat lungs.Physiological reports · 2026Article
- High altitude pulmonary hypertension: overlap with other types of pulmonary hypertension and implications for treatment.BMJ medicine · 2026Review
- DNMT1 deficiency promotes pulmonary vascular remodeling in pulmonary hypertension through epigenetic upregulation of BMP7.Respiratory research · 2025Article
- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
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- Emerging Mechanistic Insights and Therapeutic Strategies for Pulmonary Arterial Hypertension: A Focus on Right Ventricular Dysfunction and Novel Treatment Pathways.Biomedicines · 2025Review
- Review
- Exploring the pathogenesis of pulmonary vascular disease.Frontiers in medicine · 2024Review
- Chronic fetal hypoxia and antenatal Vitamin C exposure differentially regulate molecular signalling in the lung of female lambs in early adulthood.Frontiers in physiology · 2024Article
- Integrating epigenetics and metabolomics to advance treatments for pulmonary arterial hypertension.Biochemical pharmacology · 2022Review
- Stem cell therapy for pulmonary arterial hypertension: An update.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022Review
- The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude.Frontiers in cardiovascular medicine · 2022Review
- Cinaciguat (BAY-582667) Modifies Cardiopulmonary and Systemic Circulation in Chronically Hypoxic and Pulmonary Hypertensive Neonatal Lambs in the Alto Andino.Frontiers in physiology · 2022Article
- Impact of High-Altitude Hypoxia on Bone Defect Repair: A Review of Molecular Mechanisms and Therapeutic Implications.Frontiers in medicine · 2022Review
- Exposomes to Exosomes: Exosomes as Tools to Study Epigenetic Adaptive Mechanisms in High-Altitude Humans.International journal of environmental research and public health · 2021Review
- MiR-489 aggravates H2O2-induced apoptosis of cardiomyocytes via inhibiting IGF1.Bioscience reports · 2020Article
- Growth Factor Midkine Aggravates Pulmonary Arterial Hypertension via Surface Nucleolin.Scientific reports · 2020Article
- Activation of β-Catenin Signaling and its Crosstalk With Estrogen and Histone Deacetylases in Human Uterine Fibroids.The Journal of clinical endocrinology and metabolism · 2020Article
- Lysine acetyltransferases and lysine deacetylases as targets for cardiovascular disease.Nature reviews. Cardiology · 2020Review
- The Emerging Roles of Heterochromatin in Cell Migration.Frontiers in cell and developmental biology · 2020Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
High-altitude long-term hypoxia (LTH) is known to induce pulmonary arterial smooth muscle cell (PASMC) proliferation in the fetus, leading to pulmonary arterial remodeling and pulmonary hypertension of the newborn. The mechanisms underlying these conditions remain enigmatic however. We hypothesized that epigenetic alterations in fetal PASMC induced by high-altitude LTH may play an important role in modulating their proliferation during pulmonary arterial remodeling. To test this hypothesis, we have analyzed epigenetic alterations in the pulmonary vasculature of fetal lambs exposed to high-altitude LTH [pregnant ewes were kept at 3,801 m altitude from ~40 to 145 days gestation] or to sea level atmosphere. Intrapulmonary arteries were isolated, and fetal PASMC were cultured from both control and LTH fetuses. Compared with controls, in LTH fetus pulmonary arteries measurements of histone acetylation and global DNA methylation demonstrated reduced levels of global histone 4 acetylation and DNA methylation, accompanied by the loss of the cyclin-dependent kinase inhibitor p21. Treatment of LTH fetal PASMCs with histone deacetylase (HDAC) inhibitor trichostatin A decreased their proliferation rate, in part because of altered expression of p21 at both RNA and protein level. In PASMC of LTH fetuses, HDAC inhibition also decreased PDGF-induced cell migration and ERK1/2 activation and modulated global DNA methylation. On the basis of these observations, we propose that epigenetic alterations (reduced histone acetylation and DNA methylation) caused by chronic hypoxia leads to fetal PASMC proliferation and vessel remodeling associated with vascular proliferative disease and that this process is regulated by p21.
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