ArticleOncotarget2016
Loss of prolyl hydroxylase domain protein 2 in vascular endothelium increases pericyte coverage and promotes pulmonary arterial remodeling.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- Lung Pericytes: Molecular Mechanisms, Signaling Pathways, and Roles in Pulmonary Diseases.Comprehensive Physiology · 2026Review
- Deletion of GPR39 Prevents Pulmonary Arterial Hypertension by Attenuating Hypoxia-Induced Aberrant Signaling.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of BMPER Mitigates Pulmonary Hypertension by Modulating LRP1-YAP Interaction in Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- Glycolysis modulation: New therapeutic strategies to improve pulmonary hypertension (Review).International journal of molecular medicine · 2024Review
- Oxygen-sensing pathways and the pulmonary circulation.The Journal of physiology · 2024Review
- PHD1-3 oxygen sensors in vivo-lessons learned from gene deletions.Pflugers Archiv : European journal of physiology · 2024Review
- Endothelial Cell-Specific Prolyl Hydroxylase-2 Deficiency Augments Angiotensin II-Induced Arterial Stiffness and Cardiac Pericyte Recruitment in Mice.Journal of the American Heart Association · 2024Article
- Endothelial specific prolyl hydroxylase domain-containing protein 2 deficiency attenuates aging-related obesity and exercise intolerance.GeroScience · 2024Article
- A Novel Animal Model for Pulmonary Hypertension: Lung Endothelial-Specific Deletion ofJournal of respiratory biology and translational medicine · 2024Article
- Endothelial Function in Pulmonary Arterial Hypertension: From Bench to Bedside.Journal of clinical medicine · 2024Review
- A hypothesis: Potential contributions of metals to the pathogenesis of pulmonary artery hypertension.Life sciences · 2024Review
- Unraveling the role of HIF and epigenetic regulation in pulmonary arterial hypertension: implications for clinical research and its therapeutic approach.Frontiers in medicine · 2024Review
- The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension.Metabolites · 2023Review
- Endotyping COPD: hypoxia-inducible factor-2 as a molecular "switch" between the vascular and airway phenotypes?European respiratory review : an official journal of the European Respiratory Society · 2023Review
- PHD2 deletion in endothelial or arterial smooth muscle cells reveals vascular cell type-specific responses in pulmonary hypertension and fibrosis.Angiogenesis · 2022Article
- The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure.Circulation research · 2022Review
- Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases.Frontiers in pharmacology · 2022Review
- Endothelial cells in the pathogenesis of pulmonary arterial hypertension.The European respiratory journal · 2021Review
- Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders.International journal of environmental research and public health · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Pulmonary arterial hypertension (PAH) is a leading cause of heart failure. Although pulmonary endothelial dysfunction plays a crucial role in the progression of the PAH, the underlying mechanisms are poorly understood. The HIF-α hydroxylase system is a key player in the regulation of vascular remodeling. Knockout of HIF-2α has been reported to cause pulmonary hypertension. The present study examined the role of endothelial cell specific prolyl hydroxylase-2 (PHD2) in the development of PAH and pulmonary vascular remodeling. The PHD2f/f mouse was crossbred with VE-Cadherin-Cre promoter mouse to generate an endothelial specific PHD2 knockout (Cdh5-Cre-PHD2ECKO) mouse. Pulmonary arterial pressure and the size of the right ventricle was significantly elevated in the PHD2ECKO mice relative to the PHD2f/f controls. Knockout of PHD2 in EC was associated with vascular remodeling, as evidenced by an increase in pulmonary arterial media to lumen ratio and number of muscularized arterioles. The pericyte coverage and vascular smooth muscle cells were also significantly increased in the PA. The increase in vascular pericytes was associated with elevated expression of fibroblast specific protein-1 (FSP-1). Moreover, perivascular interstitial fibrosis of pulmonary arteries was significantly increased in the PHD2ECKO mice. Mechanistically, knockout of PHD2 in EC increased the expression of Notch3 and transforming growth factor (TGF-β) in the lung tissue. We conclude that the expression of PHD2 in endothelial cells plays a critical role in preventing pulmonary arterial remodeling in mice. Increased Notch3/TGF-β signaling and excessive pericyte coverage may be contributing to the development of PAH following deletion of endothelial PHD2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.