ArticleJournal of cellular physiology2018
Statin regulated ERK5 stimulates tight junction formation and reduces permeability in human cardiac endothelial cells.
Article in Journal of cellular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Intersection of Cardio-Oncology: An Overview of Radiation-Induced Heart Disease in the Context of Tumors.Journal of the American Heart Association · 2025Review
- Repurposing Atorvastatin, HMGCO-A Reductase Inhibitor, in Patients with Ulcerative Colitis: A Randomized Controlled Study.Journal of clinical medicine · 2025Article
- IFN-γ reprograms cardiac microvascular endothelial cells to mediate doxorubicin transport and influences the sensitivity of mice to doxorubicin-induced cardiotoxicity.Experimental & molecular medicine · 2025Article
- The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood-brain barrier protection.Molecular medicine (Cambridge, Mass.) · 2024Review
- The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling.International journal of molecular sciences · 2024Review
- Bone and Extracellular Signal-Related Kinase 5 (ERK5).Biomolecules · 2024Review
- Rosuvastatin Enhances Lymphangiogenesis after Myocardial Infarction by Regulating the miRNAs/Vascular Endothelial Growth Factor Receptor 3 (miRNAs/VEGFR3) Pathway.ACS pharmacology & translational science · 2024Article
- Anticancer drugs and cardiotoxicity: the role of cardiomyocyte and non-cardiomyocyte cells.Frontiers in cardiovascular medicine · 2024Review
- Micro-Executor of Natural Products in Metabolic Diseases.Molecules (Basel, Switzerland) · 2023Review
- Erk5 functions in modulation of zebrafish intestinal permeability.Cell and tissue research · 2023Article
- Recent advances in vascularized tumor-on-a-chip.Frontiers in oncology · 2023Review
- Role of non-cardiomyocytes in anticancer drug-induced cardiotoxicity: A systematic review.iScience · 2022Review
- SIRT1 activation and its effect on intercalated disc proteins as a way to reduce doxorubicin cardiotoxicity.Frontiers in pharmacology · 2022Review
- Atorvastatin Attenuates Radiotherapy-Induced Intestinal Damage through Activation of Autophagy and Antioxidant Effects.Oxidative medicine and cellular longevity · 2022Article
- A Quantitative Serum Proteomic Analysis Helps to Explore the Comprehensive Mechanism and Identify Serum Biomarkers of Shengmai Injection's Effect on Isoproterenol-Induced Myocardial Ischemia in Rats.Frontiers in pharmacology · 2021Article
- Dimethyl fumarate reduces TNF and Plasmodium falciparum induced brain endothelium activation in vitro.Malaria journal · 2020Article
- Targeting the blood-nerve barrier for the management of immune-mediated peripheral neuropathies.Experimental neurology · 2020Review
- Mechanisms of extracellular vesicle uptake in stressed retinal pigment epithelial cell monolayers.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
- Emerging Challenges of Radiation-Associated Cardiovascular Dysfunction (RACVD) in Modern Radiation Oncology: Clinical Practice, Bench Investigation, and Multidisciplinary Care.Frontiers in cardiovascular medicine · 2020Review
- MEKK3-MEK5-ERK5 signaling promotes mitochondrial degradation.Cell death discovery · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The MEKK3/MEK5/ERK5 signaling axis is required for cardiovascular development in vivo. We analyzed the physiological role of ERK5 in cardiac endothelial cells and the consequence of activation of this kinase by the statin class of HMG Co-A reductase inhibitor drugs. We utilized human cardiac microvascular endothelial cells (HCMECs) and altered ERK5 expression using siRNA mediated gene silencing or overexpression of constitutively active MEK5 and ERK5 to reveal a role for ERK5 in regulating endothelial tight junction formation and cell permeability. Statin treatment of HCMECs stimulated activation of ERK5 and translocation to the plasma membrane resulting in co-localization with the tight junction protein ZO-1 and a concomitant reduction in endothelial cell permeability. Statin mediated activation of ERK5 was a consequence of reduced isoprenoid synthesis following HMG Co-A reductase inhibition. Statin pretreatment could overcome the effect of doxorubicin in reducing endothelial tight junction formation and prevent increased permeability. Our data provide the first evidence for the role of ERK5 in regulating endothelial tight junction formation and endothelial cell permeability. Statin mediated ERK5 activation and the resulting decrease in cardiac endothelial cell permeability may contribute to the cardioprotective effects of statins in reducing doxorubicin-induced cardiotoxicity.
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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.