ArticleScience translational medicine2020
Cellular senescence impairs the reversibility of pulmonary arterial hypertension.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
What it found
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Who cites it
91 citing papers in PubMed, 134 citations in OpenAlex.
- PHLDA3 hypomethylation at the mercy of PTBP1-mediated DNMT3a decay prompts ferroptosis of cardiomyocytes to accelerate microvascular endothelial cell senescence following ischemia/reperfusion injury.Molecular and cellular biochemistry · 2026Article
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Ambient PMEnvironment & health (Washington, D.C.) · 2026Article
- E2F1 Drives Endothelial Arterial Programming in Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2026Article
- The NLRP3 Inflammasome Increases Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension.Pulmonary circulation · 2026Article
- Paradoxical Rise in Pulmonary Artery Pressure Following Successful Mavacamten Therapy for Obstructive Hypertrophic Cardiomyopathy: A Case Report.Clinical case reports · 2026Article
- The right time, the right cell: the potential for precision senotherapy in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Breaking barriers in pulmonary health of patients with metabolic diseases: senolytics and beyond.Frontiers in aging · 2026Review
- Defect in lysosomal enzyme trafficking and sorting is associated with irreversibility of pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2026Article
- CCN1-induced senescence and dysfunction of umbilical cord blood endothelial colony-forming cells in the pathogenesis of preeclampsia.Frontiers in endocrinology · 2026Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Heterogeneity of Cellular Senescence, Senotyping, and Targeting by Senolytics and Senomorphics in Lung Diseases.International journal of molecular sciences · 2025Review
- The Critical Role of HMGB1Cys106 in Regulating Sex-Specific p53 Signaling in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- Exploring the uncharted role of cell senescence in rare diseases.Orphanet journal of rare diseases · 2025Review
- Anti-ageing interventions for the treatment of cardiovascular disease.Cardiovascular research · 2025Review
- Senotherapy for chronic lung disease.Pharmacological reviews · 2025Review
- Cellular senescence in adult pulmonary hypertension: current state and future challenges.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Bioinformatics Analysis Identifies a Potential Key Gene in the Pathogenesis of Pulmonary Hypertension-HSPH1.Pulmonary circulation · 2025Article
- Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape.Expert opinion on therapeutic targets · 2025Review
- Vascular senescence and aging: mechanisms, clinical implications, and therapeutic prospects.Biogerontology · 2025Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Pulmonary arterial hypertension (PAH) in congenital cardiac shunts can be reversed by hemodynamic unloading (HU) through shunt closure. However, this reversibility potential is lost beyond a certain point in time. The reason why PAH becomes irreversible is unknown. In this study, we used MCT+shunt-induced PAH in rats to identify a dichotomous reversibility response to HU, similar to the human situation. We compared vascular profiles of reversible and irreversible PAH using RNA sequencing. Cumulatively, we report that loss of reversibility is associated with a switch from a proliferative to a senescent vascular phenotype and confirmed markers of senescence in human PAH-CHD tissue. In vitro, we showed that human pulmonary endothelial cells of patients with PAH are more vulnerable to senescence than controls in response to shear stress and confirmed that the senolytic ABT263 induces apoptosis in senescent, but not in normal, endothelial cells. To support the concept that vascular cell senescence is causal to the irreversible nature of end-stage PAH, we targeted senescence using ABT263 and induced reversal of the hemodynamic and structural changes associated with severe PAH refractory to HU. The factors that drive the transition from a reversible to irreversible pulmonary vascular phenotype could also explain the irreversible nature of other PAH etiologies and provide new leads for pharmacological reversal of end-stage PAH.
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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.