ArticleJournal of the American Heart Association2015
Endothelial p53 deletion improves angiogenesis and prevents cardiac fibrosis and heart failure induced by pressure overload in mice.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Noninvasive Positive Pressure Ventilation in Chronic Heart Failure.Canadian respiratory journal · 2016Pooled it
- Decoding the senescent endothelial landscape in ischemic stroke through single-cell and bulk RNA sequencing.Functional & integrative genomics · 2026Article
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- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2026Review
- Pulmonary Vascular Signaling in Pulmonary Hypertension: Potential Role of Endothelial CaArteriosclerosis, thrombosis, and vascular biology · 2026Review
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
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- Senescence-induced endothelial-to-mesenchymal transition accelerates the subretinal fibrosis in neovascualr age-related macular degeneration.Journal of translational medicine · 2026Article
- Pharmacological activation of p53 induces dose-dependent changes in endothelial cell fate during angiogenic sprouting.Cell death & disease · 2025Article
- Downregulation of TCF19 and ATAD2 causes endothelial cell cycle arrest at the transition from cardiac hypertrophy to heart failure.Basic research in cardiology · 2025Article
- Cellular senescence and cell therapy in cardiovascular diseases.Stem cell research & therapy · 2025Review
- Unveiling the Therapeutic Mechanisms of Chinese Herbs in Heart Failure: Integrating Network Pharmacology, Molecular Docking, and Simulation Analysis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Septin4 Regulates Cardiac Fibrosis After Pressure Overload.Circulation research · 2025Article
- Expression and function of β-site amyloid precursor protein-cleaving enzyme 2 in vascular endothelium.American journal of physiology. Heart and circulatory physiology · 2025Article
- Restoration of NOX4 signalling reverses endothelial colony-forming cell angiogenic dysfunction associated with experimental and clinical diabetes.Stem cell research & therapy · 2025Article
- CCN2 Activates Cellular Senescence Leading to Kidney Fibrosis in Folic Acid-Induced Experimental Nephropathy.International journal of molecular sciences · 2025Article
- Morphometric and Molecular Interplay in Hypertension-Induced Cardiac Remodeling with an Emphasis on the Potential Therapeutic Implications.International journal of molecular sciences · 2025Review
- Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles.Nature communications · 2025Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCardiac dysfunction developing in response to chronic pressure overload is associated with apoptotic cell death and myocardial vessel rarefaction. We examined whether deletion of tumor suppressor p53 in endothelial cells may prevent the transition from cardiac hypertrophy to heart failure. METHODS AND
resultsMice with endothelial-specific deletion of p53 (End.p53-KO) were generated by crossing p53fl/fl mice with mice expressing Cre recombinase under control of an inducible Tie2 promoter. Cardiac hypertrophy was induced by transverse aortic constriction. Serial echocardiography measurements revealed improved cardiac function in End.p53-KO mice that also exhibited better survival. Cardiac hypertrophy was associated with increased p53 levels in End.p53-WT controls, whereas banded hearts of End.p53-KO mice exhibited lower numbers of apoptotic endothelial and non-endothelial cells and altered mRNA levels of genes regulating cell cycle progression (p21), apoptosis (Puma), or proliferation (Pcna). A higher cardiac capillary density and improved myocardial perfusion was observed, and pharmacological inhibition or genetic deletion of p53 also promoted endothelial sprouting in vitro and new vessel formation following hindlimb ischemia in vivo. Hearts of End.p53-KO mice exhibited markedly less fibrosis compared with End.p53-WT controls, and lower mRNA levels of p53-regulated genes involved in extracellular matrix production and turnover (eg, Bmp-7, Ctgf, or Pai-1), or of transcription factors involved in controlling mesenchymal differentiation were observed.
conclusionsOur analyses reveal that accumulation of p53 in endothelial cells contributes to blood vessel rarefaction and fibrosis during chronic cardiac pressure overload and suggest that endothelial cells may be a therapeutic target for preserving cardiac function during hypertrophy.
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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.