ArticleCirculation research2013
De-SUMOylation enzyme of sentrin/SUMO-specific protease 2 regulates disturbed flow-induced SUMOylation of ERK5 and p53 that leads to endothelial dysfunction and atherosclerosis.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 99 citations in OpenAlex.
- Association between circulating endothelial cells and carotid atherosclerosis in patients receiving maintenance hemodialysis.BioMed research international · 2014Trial
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- UBC9-mediated p53 SUMOylation drives tubular senescence and exacerbates acute kidney injury in mice.Acta pharmacologica Sinica · 2026Article
- Integrative analysis of the expression profile and prognostic values of SENP gene family in hepatocellular carcinoma.Discover oncology · 2025Article
- The Magic and Mystery of TRIM65 in Diseases.Current medicinal chemistry · 2025Review
- Integration of multi-omics transcriptome-wide analysis for the identification of novel therapeutic drug targets in diabetic retinopathy.Journal of translational medicine · 2024Article
- The Perspectives of Platelet Proteomics in Health and Disease.Biomedicines · 2024Review
- Exploring potential targets for natural product therapy of DN: the role of SUMOylation.Frontiers in pharmacology · 2024Review
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
- An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.Circulation research · 2023Article
- The role of SUMOylation in the neurovascular dysfunction after acquired brain injury.Frontiers in pharmacology · 2023Review
- Endothelial activation and fibrotic changes are impeded by laminar flow-induced CHK1-SENP2 activity through mechanisms distinct from endothelial-to-mesenchymal cell transition.Frontiers in cardiovascular medicine · 2023Article
- Metabolic regulation of endothelial senescence.Frontiers in cardiovascular medicine · 2023Review
- Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors.Frontiers in cardiovascular medicine · 2023Review
- Crosstalk between PML and p53 in response to TGF-β1: A new mechanism of cardiac fibroblast activation.International journal of biological sciences · 2023Article
- SUMOylation targeting mitophagy in cardiovascular diseases.Journal of molecular medicine (Berlin, Germany) · 2022Review
- SENP2 Promotes VSMC Phenotypic Switching via Myocardin De-SUMOylation.International journal of molecular sciences · 2022Article
- Regulatory Non-coding RNAs in Atherosclerosis.Handbook of experimental pharmacology · 2022Review
- The role of p53 in the alternation of vascular functions.Frontiers in pharmacology · 2022Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
rationaleDisturbed flow induces proinflammatory and apoptotic responses in endothelial cells, causing them to become dysfunctional and subsequently proatherogenic.
objectiveAlthough a possible link between SUMOylation of p53 and ERK5 detected during endothelial apoptosis and inflammation has been suggested, the mechanistic insights, especially under the proatherogenic flow condition, remain largely unknown. METHODS AND
resultsSUMOylation of p53 and ERK5 was induced by disturbed flow but not by steady laminar flow. To examine the role of the disturbed flow-induced p53 and ERK5 SUMOylation, we used de-SUMOylation enzyme of sentrin/Small Ubiquitin-like MOdifier (SUMO)-specific protease 2 deficiency (Senp2(+/-)) mice and observed a significant increase in endothelial apoptosis and adhesion molecule expression both in vitro and in vivo. These increases, however, were significantly inhibited in endothelial cells overexpressing p53 and ERK5 SUMOylation site mutants. Senp2(+/-) mice exhibited increased leukocyte rolling along the endothelium, and accelerated formation of atherosclerotic lesions was observed in Senp2(+/-)/Ldlr(-/-), but not in Senp2(+/+)/Ldlr(-/-), mice fed a high-cholesterol diet. Notably, the extent of lesion size in the aortic arch of Senp2(+/-)/Ldlr(-/-) mice was much larger than that in the descending aorta, also suggesting a crucial role of the disturbed flow-induced SUMOylation of proteins, including p53 and ERK5 in atherosclerosis formation.
conclusionsThese data show the unique role of sentrin/SUMO-specific protease 2 on endothelial function under disturbed flow and suggest that SUMOylation of p53 and ERK5 by disturbed flow contributes to the atherosclerotic plaque formation. Molecules involved in this newly discovered signaling will be useful targets for controlling endothelial cells dysfunction and consequently atherosclerosis formation.
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