ArticleAging2015
Role of p38 mitogen-activated protein kinase in vascular endothelial aging: interaction with Arginase-II and S6K1 signaling pathway.
Article in Aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- The Janus face of L-arginine supplementation in cardiovascular health and aging exploration of underlying mechanisms.Frontiers in aging · 2026Review
- Is Senolytic Therapy in Cardiovascular Diseases Ready for Translation to Clinics?Biomolecules · 2025Review
- Pathophysiology of Arginases in Cancer and Efforts in Their Pharmacological Inhibition.International journal of molecular sciences · 2024Review
- Role of platelet factor 4 in arteriovenous fistula maturation failure: What do we know so far?The journal of vascular access · 2024Review
- Myo1b Promotes Premature Endothelial Senescence and Dysfunction via Suppressing Autophagy: Implications for Vascular Aging.Oxidative medicine and cellular longevity · 2023Article
- Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang.Frontiers in pharmacology · 2023Article
- Arginase 2 negatively regulates sorafenib-induced cell death by mediating ferroptosis in melanoma.Acta biochimica et biophysica Sinica · 2022Article
- Arginase: shedding light on the mechanisms and opportunities in cardiovascular diseases.Cell death discovery · 2022Review
- Virtual Screening for FDA-Approved Drugs That Selectively Inhibit Arginase Type 1 and 2.Molecules (Basel, Switzerland) · 2022Article
- Significance of neutrophil microparticles in ischaemia-reperfusion: Pro-inflammatory effectors of endothelial senescence and vascular dysfunction.Journal of cellular and molecular medicine · 2020Article
- FASN activity is important for the initial stages of the induction of senescence.Cell death & disease · 2019Article
- Where Metabolism Meets Senescence: Focus on Endothelial Cells.Frontiers in physiology · 2019Review
- The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells.Oncotarget · 2017Review
- Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6.Scientific reports · 2017Article
- Role of circulating factors in cardiac aging.Journal of thoracic disease · 2017Review
- Premature senescence of endothelial cells upon chronic exposure to TNFα can be prevented by N-acetyl cysteine and plumericin.Scientific reports · 2017Article
- Arginase-II Deficiency Extends Lifespan in Mice.Frontiers in physiology · 2017Article
- Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases.Radiation research · 2016Review
- Vascular Fibrosis in Aging and Hypertension: Molecular Mechanisms and Clinical Implications.The Canadian journal of cardiology · 2016Review
- Anti-TNF-α treatment modulates SASP and SASP-related microRNAs in endothelial cells and in circulating angiogenic cells.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p38 mitogen-activated protein kinase (p38) regulates cellular senescence and senescence-associated secretory phenotype (SASP), i.e., secretion of cytokines and/or chemokines. Previous work showed that augmented arginase-II (Arg-II) and S6K1 interact with each other to promote endothelial senescence through uncoupling of endothelial nitric oxide synthase (eNOS). Here we demonstrate eNOS-uncoupling, augmented expression/secretion of IL-6 and IL-8, elevation of p38 activation and Arg-II levels in senescent endothelial cells. Silencing Arg-II or p38α in senescent cells recouples eNOS and inhibits IL-6 and IL-8 secretion. Overexpression of Arg-II in young endothelial cells causes eNOS-uncoupling and enhances IL-6 and IL-8 expression/secretion, which is prevented by p38 inhibition or by antioxidant. Moreover, p38 activation and expression of IL-6 and KC (the murine IL-8 homologue) are increased in the heart and/or aortas of wild type (WT) old mice, which is abolished in mice with Arg-II gene deficiency (Arg-II-/-). In addition, inhibition of p38 in the old WT mice recouples eNOS function and reduces IL-6 and KC expression in the aortas and heart. Silencing Arg-II or p38a or S6K1 inhibits each other in senescence endothelial cells. Thus, Arg-II, p38, and S6K1 form a positive circuit which regulates endothelial senescence and cardiovascular aging.
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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.