ArticleArteriosclerosis, thrombosis, and vascular biology2025
High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- GLSP ameliorates monocrotaline-induced pulmonary arterial hypertension through inhibition of the PI3K/AKT and MAPK signaling pathways.Journal of molecular histology · 2026Article
- Endothelial Continuum and Capillary Specialization in Pulmonary Vascular Development.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- ERG preserves endothelial identity to limit atherosclerosis.Nature communications · 2026Article
- Haemodynamic alterations associated with hepatic vascular malformations in hereditary haemorrhagic telangiectasia: A cohort study.JHEP reports : innovation in hepatology · 2026Article
- Integrative multi-omics and machine learning reveal glycolysis-related biomarkers driving vascular remodeling in pulmonary arterial hypertension.Molecular and cellular biochemistry · 2026Article
- Chronic Thromboembolic Pulmonary Hypertension as an Inflammation-Angiogenesis Disorder: From Thrombus Persistence to Dual Pulmonary Vasculopathy.Reviews in cardiovascular medicine · 2026Review
- Identification of drug candidates for rescue of SOX17 gene targets in pulmonary arterial hypertension.bioRxiv : the preprint server for biology · 2026Article
- ERG is a regulator of dynamic and reversible endothelial plasticity.Genome medicine · 2026Article
- ERG-deficient endothelium identifies IL-8/CXCR2 axis as a therapeutic target for resolving neutrophilic lung vascular injury.JCI insight · 2026Article
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- A second-hit conceptual framework for pulmonary arterial hypertension in adult congenital heart disease: genetics, hemodynamics, and treat-and-repair.Frontiers in cardiovascular medicine · 2026Review
- Endothelial Heterogeneity in Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Current Evidence on the Potential Role of EndothelialReviews in cardiovascular medicine · 2026Review
- A Brief Overview of Biomechanics and Mechanobiology of the Pulmonary Circulation.Advances in experimental medicine and biology · 2026Review
- Yes-associated protein 1 in cancer: bridging mechanical transduction and epigenetic regulation.Cancer biology & therapy · 2025Review
- Endothelial to mesenchymal transition: a central mechanism in diabetes-induced vascular pathology.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- From development to regeneration: the endothelial interface in lung injury and repair.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Pulmonary Artery Shear Stress and Oscillatory Shear Index are Associated with Right Ventricular Remodeling in Repaired Tetralogy of Fallot.Annals of biomedical engineering · 2025Article
- Pressure Points: Endothelial Responses to Shear Stress and Pressure in Health and Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2025Article
- Fluid Shear Stress-Regulated Vascular Remodeling: Past, Present, and Future.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
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24 authors.
Funding
Abstract
backgroundComputational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm
methodsWe used the Ibidi perfusion system to determine whether HSS applied to human PA endothelial cells (ECs) induces EndMT when compared with physiological laminar shear stress (15 dyn/cm
resultsEndMT, a feature of PAH not previously attributed to HSS, was observed. HSS did not alter the induction of transcription factors KLF (Krüppel-like factor) 2/4, but an ERG (ETS-family transcription factor) was reduced, as were histone H3 lysine 27 acetylation enhancer-promoter peaks containing ERG motifs. Consequently, there was reduced interaction between ERG and KLF2/4, a feature important in tethering KLF and the chromatin remodeling complex to DNA. In PA ECs under laminar shear stress, reducing ERG by siRNA caused EndMT associated with decreased BMPR2 (bone morphogenetic protein receptor 2), CDH5 (cadherin 5), and PECAM1 (platelet and EC adhesion molecule 1) and increased SNAI1/2 (Snail/Slug) and ACTA2 (smooth muscle α2 actin). In PA ECs under HSS, transfection of ERG prevented EndMT. HSS was then induced in mice by an aortocaval shunt, causing progressive PAH over 8 weeks. An adeno-associated viral vector (AAV2-ESGHGYF) was used to replenish ERG selectively in PA ECs. Elevated PA pressure, EndMT, and vascular remodeling (muscularization of peripheral arteries) in the aortocaval shunt mice were markedly reduced by ERG delivery.
conclusionsPathological HSS reduced lung EC ERG, resulting in EndMT and PAH. Agents that upregulate ERG could reverse HSS-mediated PAH and occlusive vascular remodeling resulting from high flow or narrowed PAs.
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