ArticlePhysiological reports2019
Altered hypoxia-inducible factor-1α (HIF-1α) signaling contributes to impaired angiogenesis in fetal lambs with persistent pulmonary hypertension of the newborn (PPHN).
Article in Physiological reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- LncRNA H19 Promotes Angiogenesis in Mouse Pulmonary Artery Endothelial Cells by Regulating the HIF-1α/VEGF Signaling Pathway.Biochemical genetics · 2025Article
- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
- The FKBPL-based therapeutic peptide, AD-01, protects the endothelium from hypoxia-induced damage by stabilising hypoxia inducible factor-α and inflammation.Journal of translational medicine · 2025Article
- Hypoxia-induced pulmonary hypertension in adults and newborns: implications for drug development.Drug discovery today · 2024Review
- Exploring the pathogenesis of pulmonary vascular disease.Frontiers in medicine · 2024Review
- Mitochondrial Regulation of the Hypoxia-Inducible Factor in the Development of Pulmonary Hypertension.Journal of clinical medicine · 2022Review
- The glycolytic process in endothelial cells and its implications.Acta pharmacologica Sinica · 2022Review
- Sildenafil protects against pulmonary hypertension induced by hypoxia in neonatal rats via activation of PPARγ‑mediated downregulation of TRPC.International journal of molecular medicine · 2022Article
- Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Review
- Decreased Cyclic Guanosine Monophosphate-Protein Kinase G Signaling Impairs Angiogenesis in a Lamb Model of Persistent Pulmonary Hypertension of the Newborn.American journal of respiratory cell and molecular biology · 2021Article
- Pediatric Pulmonary Hypertension: Definitions, Mechanisms, Diagnosis, and Treatment.Comprehensive Physiology · 2021Article
- AMP-Kinase Dysfunction Alters Notch Ligands to Impair Angiogenesis in Neonatal Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2020Article
- Altered hypoxia-inducible factor-1α (HIF-1α) signaling contributes to impaired angiogenesis in fetal lambs with persistent pulmonary hypertension of the newborn (PPHN).Physiological reports · 2019Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Previous studies in adult pulmonary hypertension reported that increased hypoxia-inducible factor-1α (HIF-1α) signaling contributes to pulmonary vascular remodeling. However, alterations in endothelial HIF-1α signaling and its contribution to impaired angiogenesis in persistent pulmonary hypertension of the newborn (PPHN) remain unclear. We investigated the hypothesis that HIF-1α levels are increased in lung endothelial cells in PPHN and contribute to impaired angiogenesis function. We examined HIF-1α expression and promoter activity in the isolated pulmonary artery endothelial cells (PAEC) from fetal lambs with or without PPHN induced by prenatal ductus arteriosus constriction. We measured the levels of HIF-1α downstream targets, vascular endothelial growth factor (VEGF) and glycolytic protein, hexokinase 2 (Hek-2) in PAEC from PPHN, and control lambs. We examined the effect of small interfering-RNA (siRNA) mediated knockdown of native HIF-1α on VEGF expression and in vitro angiogenesis function of PPHN-PAEC. HIF-1α protein levels were higher in the isolated PAEC from PPHN-lambs compared to controls. HIF-1α promoter activity and Hek-2 protein levels were higher in PPHN. VEGF protein levels and in vitro angiogenesis function were decreased in PAEC from PPHN lambs. HIF-1α silencing significantly increased the expression of VEGF and improved the angiogenesis function of PPHN PAEC. Aberrant HIF-1α signaling contributes to endothelial dysfunction and decreased angiogenesis in PPHN.
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