ArticleCirculation research2020
B55α/PP2A Limits Endothelial Cell Apoptosis During Vascular Remodeling: A Complementary Approach To Disrupt Pathological Vessels?
Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Surfactant protein A deficiency aggravates silica-induced pulmonary fibrosis by promoting intrinsic apoptosis of alveolar type II epithelial cells.Respiratory research · 2026Article
- PP2Acα Deficiency in Vascular Smooth Muscle Cells Accelerates Aortic Aneurysm and Dissection by Regulating KLF4 Phosphorylation and Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α.npj metabolic health and disease · 2024Article
- Etrinabdione (VCE-004.8), a B55α activator, promotes angiogenesis and arteriogenesis in critical limb ischemia.Journal of translational medicine · 2024Article
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- Neuroprotective Efficacy of Betulinic Acid Hydroxamate, a B55α/PP2A Activator, in Acute Hypoxia-Ischemia-Induced Brain Damage in Newborn Rats.Translational stroke research · 2023Article
- Hsa-miR-409-3p regulates endothelial progenitor senescence via PP2A-P38 and is a potential ageing marker in humans.Journal of cellular and molecular medicine · 2023Article
- Hydroxysafflower Yellow A Inhibits Vascular Adventitial Fibroblast Migration via NLRP3 Inflammasome Inhibition through Autophagy Activation.International journal of molecular sciences · 2022Article
- Neuroprotective Effects of Betulinic Acid Hydroxamate in Intraventricular Hemorrhage-Induced Brain Damage in Immature Rats.Nutrients · 2022Article
- Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability.Nature communications · 2022Article
- A cannabidiol aminoquinone derivative activates the PP2A/B55α/HIF pathway and shows protective effects in a murine model of traumatic brain injury.Journal of neuroinflammation · 2022Article
- Manipulation of the crosstalk between tumor angiogenesis and immunosuppression in the tumor microenvironment: Insight into the combination therapy of anti-angiogenesis and immune checkpoint blockade.Frontiers in immunology · 2022Review
- Molecular mechanisms of endothelial dysfunction in Kawasaki-disease-associated vasculitis.Frontiers in cardiovascular medicine · 2022Review
- Allosteric activation of PP2A inhibits experimental abdominal aortic aneurysm.Clinical science (London, England : 1979) · 2021Article
- Betulinic Acid Hydroxamate is Neuroprotective and Induces Protein Phosphatase 2A-Dependent HIF-1α Stabilization and Post-transcriptional Dephosphorylation of Prolyl Hydrolase 2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Apoptosis in resistance arteries induced by hydrogen peroxide: greater resilience of endothelium versus smooth muscle.American journal of physiology. Heart and circulatory physiology · 2021Review
- Protein Phosphatase 2A Deficiency in Macrophages Increases Foam Cell Formation and Accelerates Atherosclerotic Lesion Development.Frontiers in cardiovascular medicine · 2021Article
- Biphasic Effect of Pirfenidone on Angiogenesis.Frontiers in pharmacology · 2021Article
- Protein Phosphatase 2A Mediates YAP Activation in Endothelial Cells Upon VEGF Stimulation and Matrix Stiffness.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
- Commented on by
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
rationaleHow endothelial cells (ECs) migrate and form an immature vascular plexus has been extensively studied. Yet, mechanisms underlying vascular remodeling remain poorly established. A better understanding of these processes may lead to the design of novel therapeutic strategies complementary to current angiogenesis inhibitors.
objectiveStarting from our previous observations that PP2A (protein phosphatase 2) regulates the HIF (hypoxia-inducible factor)/PHD-2 (prolyl hydroxylase 2)-constituted oxygen machinery, we hypothesized that this axis could play an important role during blood vessel formation, tissue perfusion, and oxygen restoration. METHODS AND
resultsWe show that the PP2A regulatory subunit B55α is at the crossroad between vessel pruning and vessel maturation. Blood vessels with high B55α counter cell stress conditions and thrive for stabilization and maturation. When B55α is inhibited, ECs cannot cope with cell stress and undergo apoptosis, leading to massive pruning of nascent blood vessels. Mechanistically, we found that the B55α/PP2A complex restrains PHD-2 activity, promoting EC survival in a HIF-dependent manner, and furthermore dephosphorylates p38, altogether protecting ECs against cell stress occurring, for example, during the onset of blood flow. In tumors, EC-specific B55α deficiency induces pruning of immature-like tumor blood vessels resulting in delayed tumor growth and metastasis, without affecting nonpathological vessels. Consistently, systemic administration of a pan-PP2A inhibitor disrupts vascular network formation and tumor progression in vivo without additional effects on B55α-deficient vessels.
conclusionsOur data underline a unique role of the B55α/PP2A phosphatase complex in vessel remodeling and suggest the use of PP2A-inhibitors as potent antiangiogenic drugs targeting specifically nascent blood vessels with a mode-of-action complementary to VEGF-R (vascular endothelial growth factor receptor)-targeted therapies. Graphical Abstract: A graphical abstract is available for this article.
Indexed as
Identifiers
What OpenQuestion holds
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.