ArticleJournal of cellular and molecular medicine2019
Inhibition of P53/miR-34a improves diabetic endothelial dysfunction via activation of SIRT1.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- ORMDL3 as Key Regulator of Endothelial Dysfunction in Atherosclerosis via Sphingolipid Biosynthesis.Inflammation · 2026Article
- Small RNA sequencing of human sural nerves identifies widespread microRNA dysregulation and Schwann cell-localized miR-21-5p in diabetic peripheral neuropathy.bioRxiv : the preprint server for biology · 2026Article
- Restoration of NOX4 signalling reverses endothelial colony-forming cell angiogenic dysfunction associated with experimental and clinical diabetes.Stem cell research & therapy · 2025Article
- SIRT1 and miR-34a as Potential Plasma Biomarkers in the Acute Phase of Ischemic Stroke.International journal of molecular and cellular medicine · 2025Article
- MiRNA-34a, miRNA-145, and miRNA-222 Expression, Matrix Metalloproteinases, TNF-α and VEGF in Patients with Different Phenotypes of Coronary Artery Disease.International journal of molecular sciences · 2024Observational
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- Review
- Review
- miR34a-5p impedes CLOCK expression in chronodisruptive C57BL/6J mice and potentiates pro-atherogenic manifestations.PloS one · 2023Article
- MicroRNAs as Biomarkers for Coronary Artery Disease Related to Type 2 Diabetes Mellitus-From Pathogenesis to Potential Clinical Application.International journal of molecular sciences · 2022Review
- Oxidative Stress and Inflammation in Cardiovascular Diseases and Cancer: Role of Non-coding RNAs.The Yale journal of biology and medicine · 2022Review
- Tetrahydroxy stilbene glycoside attenuates endothelial cell premature senescence induced by HScientific reports · 2022Article
- MicroRNA-34a in coronary heart disease: Correlation with disease risk, blood lipid, stenosis degree, inflammatory cytokines, and cell adhesion molecules.Journal of clinical laboratory analysis · 2022Article
- The role of p53 in the alternation of vascular functions.Frontiers in pharmacology · 2022Review
- MicroRNA-34a: the bad guy in age-related vascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Inflammatory Mechanisms Contributing to Endothelial Dysfunction.Biomedicines · 2021Review
- Dihydromyricetin Alleviates High Glucose-Induced Oxidative Stress and Apoptosis in Human Retinal Pigment Epithelial Cells by Downregulating miR-34a Expression.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- A novel role of kallikrein-related peptidase 8 in the pathogenesis of diabetic cardiac fibrosis.Theranostics · 2021Article
- The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress.International journal of molecular sciences · 2020Review
- Protective role of NRF2 in macrovascular complications of diabetes.Journal of cellular and molecular medicine · 2020Review
Corrections and comments
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Authors and funding
8 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial dysfunction contributes to diabetic macrovascular complications, resulting in high mortality. Recent findings demonstrate a pathogenic role of P53 in endothelial dysfunction, encouraging the investigation of the effect of P53 inhibition on diabetic endothelial dysfunction. Thus, high glucose (HG)-treated endothelial cells (ECs) were subjected to pifithrin-α (PFT-α)-a specific inhibitor of P53, or P53-small interfering RNA (siRNA), both of which attenuated the HG-induced endothelial inflammation and oxidative stress. Moreover, inhibition of P53 by PFT-α or P53-siRNA prohibited P53 acetylation, decreased microRNA-34a (miR-34a) level, leading to a dramatic increase in sirtuin 1 (SIRT1) protein level. Interestingly, the miR-34a inhibitor (miR-34a-I) and PFT-α increased SIRT1 protein level and alleviated the HG-induced endothelial inflammation and oxidative stress to a similar extent; however, these effects of PFT-α were completely abrogated by the miR-34a mimic. In addition, SIRT1 inhibition by EX-527 or Sirt1-siRNA completely abolished miR-34a-I's protection against HG-induced endothelial inflammation and oxidative stress. Furthermore, in the aortas of streptozotocin-induced diabetic mice, both PFT-α and miR-34a-I rescued the inflammation, oxidative stress and endothelial dysfunction caused by hyperglycaemia. Hence, the present study has uncovered a P53/miR-34a/SIRT1 pathway that leads to endothelial dysfunction, suggesting that P53/miR-34a inhibition could be a viable strategy in the management of diabetic macrovascular diseases.
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Registered trials
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