ArticleCardiovascular research2022
Targeting RUNX1 as a novel treatment modality for pulmonary arterial hypertension.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Targeting Runx1 Slows Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Bellidifolin Improves Pulmonary Artery Smooth Muscle Cells Proliferation by Targeting the IGFBP5-Mediated PI3K-AKT-mTOR Pathway and Dilates the Pulmonary Artery.Biomolecules · 2026Article
- The critical role of the RUNX1/NF-κB transcriptional complex-mediated PVAT-VSMC axis in aortic dissection.Journal of cardiothoracic surgery · 2026Review
- Article
- Runx1-Snx9 axis drives the pathological secretion of mitochondrial-derived vesicles to activate cGAS-STING signaling in acute pancreatitis.Journal of nanobiotechnology · 2026Article
- Identification of RUNX1 as a Biomarker for Right Ventricular Remodeling in Pulmonary Arterial Hypertension Using WGCNA.Pulmonary circulation · 2026Article
- Identification of drug candidates for rescue of SOX17 gene targets in pulmonary arterial hypertension.bioRxiv : the preprint server for biology · 2026Article
- RUNX1 is expressed in a subpopulation of dermal fibroblasts and is associated with disease severity of systemic sclerosis.Annals of the rheumatic diseases · 2026Article
- Article
- The Dual Role of RUNX1 in Inflammation-Driven Age-Related Diseases: From Molecular Mechanisms to Clinical Translation.Biomedicines · 2025Review
- Longitudinal Multi-Organ Transcriptomic Atlas of Salt-Induced Hypertension.bioRxiv : the preprint server for biology · 2025Article
- MicroRNA-210 Mediates Hypoxic Pulmonary Hypertension in the Newborn Lamb.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Inhibition of RUNX1 slows the progression of pulmonary hypertension by targeting CBX5.Biomolecules & biomedicine · 2025Article
- Macrophage-driven immunopathology in pulmonary arterial hypertension: from mechanisms to targeted therapies.Frontiers in immunology · 2025Review
- Runt-related transcription factors: from pathogenesis to therapeutic targets in multiple-organ fibrosis.Frontiers in cell and developmental biology · 2025Review
- T follicular helper cell is essential for M2 macrophage polarization and pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension.Respiratory research · 2024Article
- MicroRNA-210 mediates hypoxia-induced pulmonary hypertension by targeting mitochondrial bioenergetics and mtROS flux.Acta physiologica (Oxford, England) · 2024Article
- Immunotherapy for Pulmonary Arterial Hypertension: From the Pathogenesis to Clinical Management.International journal of molecular sciences · 2024Review
- The role of RUNX1/NF-κB in regulating PVAT inflammation in aortic dissection.Scientific reports · 2024Article
- Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension.Respiratory research · 2024Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
aimsPulmonary arterial hypertension (PAH) is a fatal disease without a cure. Previously, we found that transcription factor RUNX1-dependent haematopoietic transformation of endothelial progenitor cells may contribute to the pathogenesis of PAH. However, the therapeutic potential of RUNX1 inhibition to reverse established PAH remains unknown. In the current study, we aimed to determine whether RUNX1 inhibition was sufficient to reverse Sugen/hypoxia (SuHx)-induced pulmonary hypertension (PH) in rats. We also aimed to demonstrate possible mechanisms involved. METHODS AND
resultsWe administered a small molecule specific RUNX1 inhibitor Ro5-3335 before, during, and after the development of SuHx-PH in rats to investigate its therapeutic potential. We quantified lung macrophage recruitment and activation in vivo and in vitro in the presence or absence of the RUNX1 inhibitor. We generated conditional VE-cadherin-CreERT2; ZsGreen mice for labelling adult endothelium and lineage tracing in the SuHx-PH model. We also generated conditional Cdh5-CreERT2; Runx1(flox/flox) mice to delete Runx1 gene in adult endothelium and LysM-Cre; Runx1(flox/flox) mice to delete Runx1 gene in cells of myeloid lineage, and then subjected these mice to SuHx-PH induction. RUNX1 inhibition in vivo effectively prevented the development, blocked the progression, and reversed established SuHx-induced PH in rats. RUNX1 inhibition significantly dampened lung macrophage recruitment and activation. Furthermore, lineage tracing with the inducible VE-cadherin-CreERT2; ZsGreen mice demonstrated that a RUNX1-dependent endothelial to haematopoietic transformation occurred during the development of SuHx-PH. Finally, tissue-specific deletion of Runx1 gene either in adult endothelium or in cells of myeloid lineage prevented the mice from developing SuHx-PH, suggesting that RUNX1 is required for the development of PH.
conclusionBy blocking RUNX1-dependent endothelial to haematopoietic transformation and pulmonary macrophage recruitment and activation, targeting RUNX1 may be as a novel treatment modality for pulmonary arterial hypertension.
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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 Socratic graph.