ArticleAmerican journal of respiratory and critical care medicine2016
Role for Runt-related Transcription Factor 2 in Proliferative and Calcified Vascular Lesions in Pulmonary Arterial Hypertension.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03655704 (Apabetalone for Pulmonary Arterial Hypertension), which is not on this map. Cited by 62 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study
Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
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- Decoding vascular calcification: mechanistic insights and translational strategies.Cellular and molecular life sciences : CMLS · 2026Review
- Super enhancer-driven LINC01013 mediates hypoxia-induced mitochondrial dysfunction by HSPA9 to determine pulmonary arterial smooth muscle cell fate.Cellular and molecular life sciences : CMLS · 2026Article
- Post-translational modification of transcription factors: perspectives in vascular medicine.Cell death & disease · 2025Review
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- MicroRNA in pediatric pulmonary hypertension microRNA profiling to inform disease classification, severity, and treatment response in pediatric pulmonary hypertension.American journal of physiology. Heart and circulatory physiology · 2025Article
- GTX-11 attenuates lung fibrosis, inflammation and vascular remodeling in preclinical models of lung fibrotic disease.Frontiers in pharmacology · 2025Article
- Axonal Energy Crisis and Calcium Phosphate Dysregulation as Pathogenesis of Optic Disc Drusen.Aging and disease · 2024Review
- Identification and Validation of the miR/RAS/RUNX2 Autophagy Regulatory Network in AngII-Induced Hypertensive Nephropathy in MPC5 Cells Treated with Hydrogen Sulfide Donors.Antioxidants (Basel, Switzerland) · 2024Article
- Exosomes enriched by miR-429-3p derived from ITGB1 modified Telocytes alleviates hypoxia-induced pulmonary arterial hypertension through regulating Rac1 expression.Cell biology and toxicology · 2024Article
- Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.International journal of medical sciences · 2024Review
- Review
- Epigenetic Reader Bromodomain-Containing Protein 4 in Aging-Related Vascular Pathologies and Diseases: Molecular Basis, Functional Relevance, and Clinical Potential.Biomolecules · 2023Review
- Role of prolyl hydroxylase/HIF-1 signaling in vascular calcification.Clinical kidney journal · 2023Review
- Transcription factors and potential therapeutic targets for pulmonary hypertension.Frontiers in cell and developmental biology · 2023Review
- Nebulization of extracellular vesicles: A promising small RNA delivery approach for lung diseases.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Hypoxia-inducible factor signaling in vascular calcification in chronic kidney disease patients.Journal of nephrology · 2022Review
- IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis.Respiratory research · 2022Article
- HNRNPA2B1: RNA-Binding Protein That Orchestrates Smooth Muscle Cell Phenotype in Pulmonary Arterial Hypertension.Circulation · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
Abstract
rationalePulmonary arterial hypertension (PAH) is characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This is sustained in time by the down-regulation of microRNA (miR)-204. In systemic vascular diseases, reduced miR-204 expression promotes vascular biomineralization by augmenting the expression of the transcription factor Runt-related transcription factor 2 (RUNX2). Implication of RUNX2 in PAH-related vascular remodeling and presence of calcified lesions in PAH remain unexplored.
objectivesWe hypothesized that RUNX2 is up-regulated in lungs of patients with PAH, contributing to vascular remodeling and calcium-related biomineralization.
methodsWe harvested human lung tissues in which we assessed calcification lesions and RUNX2 expression. We also isolated PASMCs from these tissues for in vitro analyses. Using a bidirectional approach, we investigated the role for RUNX2 in cell proliferation, apoptosis, and calcification capacity. Ectopic delivery of small interfering RNA against RUNX2 was used in an animal model of PAH to evaluate the therapeutic potential of RUNX2 inhibition in this disease. MEASUREMENTS AND MAIN
resultsPatients with PAH display features of calcified lesions within the distal pulmonary arteries (PAs). We show that RUNX2 is up-regulated in lungs, distal PAs, and primary cultured human PASMCs isolated from PAH and compared with patients without PAH. RUNX2 expression histologically correlates with vascular remodeling and calcification. Using in vitro gain- and loss-of-function approaches, we mechanistically demonstrate that miR-204 diminution promotes RUNX2 up-regulation and that sustained RUNX2 expression activates hypoxia-inducible factor-1α, leading to aberrant proliferation, resistance to apoptosis, and subsequent transdifferentiation of PAH-PASMCs into osteoblast-like cells. In the PAH Sugen/hypoxia rat model, molecular RUNX2 inhibition reduces PA remodeling and prevents calcification, thus improving pulmonary hemodynamic parameters and right ventricular function.
conclusionsRUNX2 plays a pivotal role in the pathogenesis of PAH, contributing to the development of proliferative and calcified PA lesions. Inhibition of RUNX2 may therefore represent an attractive therapeutic strategy for PAH.
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