ArticleCirculation2013
Activation of lung p53 by Nutlin-3a prevents and reverses experimental pulmonary hypertension.
Article in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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Who cites it
64 citing papers in PubMed, 111 citations in OpenAlex.
- Emerging significance of E3 ubiquitin ligases and Deubiquitinases in pulmonary hypertension.Molecular medicine (Cambridge, Mass.) · 2026Review
- Cellular senescence and cell therapy in cardiovascular diseases.Stem cell research & therapy · 2025Review
- Advanced cancer therapy: unlocking the potential of small molecule inhibitors.Future medicinal chemistry · 2025Review
- Unraveling the meta-hallmarks between senescent and tumor cells: A new perspective for senolytic drug discovery.Acta pharmaceutica Sinica. B · 2025Review
- Cellular senescence in adult pulmonary hypertension: current state and future challenges.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Review
- Unraveling AURKB as a potential therapeutic target in pulmonary hypertension using integrated transcriptomic analysis and pre-clinical studies.Cell reports. Medicine · 2025Article
- Melk facilitates pulmonary artery smooth muscle cell proliferation and migration in pulmonary hypertension via modulation of YAP/TAZ signaling.Frontiers in cell and developmental biology · 2025Article
- Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis.Cell communication and signaling : CCS · 2024Article
- Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.Circulation · 2024Article
- Biphasic regulation of miR-17∼92 transcription during hypoxia: roles of HIF1 and p53 hyperphosphorylation at ser15.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- A hypothesis: Potential contributions of metals to the pathogenesis of pulmonary artery hypertension.Life sciences · 2024Review
- Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity.Nature communications · 2023Article
- NDRG1 promotes endothelial dysfunction and hypoxia-induced pulmonary hypertension by targeting TAF15.Precision clinical medicine · 2023Article
- DNA nanoparticles targeting FOXO4 selectively eliminate cigarette smoke-induced senescent lung fibroblasts.Nanoscale advances · 2023Article
- Genome-wide CRISPR screening reveals ADCK3 as a key regulator in sensitizing endometrial carcinoma cells to MPA therapy.British journal of cancer · 2023Article
- Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.MedComm · 2023Review
- Therapeutic opportunities for senolysis in cardiovascular disease.The FEBS journal · 2023Review
- Article
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4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInduction of cellular senescence through activation of the p53 tumor suppressor protein is a new option for treating proliferative disorders. Nutlins prevent the ubiquitin ligase MDM2 (murine double minute 2), a negative p53 regulator, from interacting with p53. We hypothesized that cell senescence induced by Nutlin-3a exerted therapeutic effects in pulmonary hypertension (PH) by limiting the proliferation of pulmonary artery smooth muscle cells (PA-SMCs). METHODS AND
resultsNutlin-3a treatment of cultured human PA-SMCs resulted in cell growth arrest with the induction of senescence but not apoptosis; increased phosphorylated p53 protein levels; and expression of p53 target genes including p21, Bax, BTG2, and MDM2. Daily intraperitoneal Nutlin-3a treatment for 3 weeks dose-dependently reduced PH, right ventricular hypertrophy, and distal pulmonary artery muscularization in mice exposed to chronic hypoxia or SU5416/hypoxia. Nutlin-3a treatment also partially reversed PH in chronically hypoxic or transgenic mice overexpressing the serotonin-transporter in SMCs (SM22-5HTT+ mice). In these mouse models of PH, Nutlin-3a markedly increased senescent p21-stained PA-SMCs; lung p53, p21, and MDM2 protein levels; and p21, Bax, PUMA, BTG2, and MDM2 mRNA levels; but induced only minor changes in control mice without PH. Marked MDM2 immunostaining was seen in both mouse and human remodeled pulmonary vessels, supporting the use of Nutlins as a PH-targeted therapy. PH prevention or reversal by Nutlin-3a required lung p53 stabilization and increased p21 expression, as indicated by the absence of Nutlin-3a effects in hypoxia-exposed p53(-/-) and p21(-/-) mice.
conclusionsNutlin-3a may hold promise as a prosenescence treatment targeting PA-SMCs in PH.
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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.