ArticlePloS one2014
Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 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
29 citing papers in PubMed, 49 citations in OpenAlex.
- miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease.Circulation research · 2017Trial
- HIV vasculopathy: role of mononuclear cell-associated Krüppel-like factors 2 and 4.AIDS (London, England) · 2015Trial
- The KLF4-CD46 axis: a novel therapeutic target in transplant-associated thrombotic microangiopathy and beyond.Haematologica · 2026Article
- Molecular hallmarks of excitatory and inhibitory neuronal resilience to Alzheimer's disease.Molecular neurodegeneration · 2025Article
- Atherosclerosis-induced arterial erectile dysfunction: pathogenesis, diagnosis, and therapeutic strategies.Translational andrology and urology · 2025Review
- KLF family members control expression of genes required for tissue macrophage identities.The Journal of experimental medicine · 2025Article
- Article
- Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.Acta pharmacologica Sinica · 2024Review
- Recent advances of mechanosensitive genes in vascular endothelial cells for the formation and treatment of atherosclerosis.Genes & diseases · 2024Review
- Krüppel-like Factor (KLF) family members control expression of genes required for serous cavity and alveolar macrophage identities.bioRxiv : the preprint server for biology · 2024Article
- Transcription factors regulating vasculogenesis and angiogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Review
- Drug mechanism enrichment analysis improves prioritization of therapeutics for repurposing.BMC bioinformatics · 2023Article
- Dysregulation of Krüppel-like Factor 2 and Myocyte Enhancer Factor 2D Drive Cardiac Microvascular Inflammation and Dysfunction in Diabetes.International journal of molecular sciences · 2023Article
- TGFβ signaling pathways in human health and disease.Frontiers in molecular biosciences · 2023Review
- Epigenetic Regulation of Endothelial Cell Lineages During Zebrafish Development-New Insights From Technical Advances.Frontiers in cell and developmental biology · 2022Review
- Bone marrow stromal cell antigen-1 (CD157) regulated by sphingosine kinase 2 mediates kidney fibrosis.Frontiers in medicine · 2022Article
- The MEK5/ERK5 Pathway in Health and Disease.International journal of molecular sciences · 2021Review
- MEF2 (Myocyte Enhancer Factor 2) Is Essential for Endothelial Homeostasis and the Atheroprotective Gene Expression Program.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Activation of TWIST Transcription by Chromatin Remodeling Protein BRG1 Contributes to Liver Fibrosis in Mice.Frontiers in cell and developmental biology · 2020Article
- Atheroprotective Flow Upregulates ITPR3 (Inositol 1,4,5-Trisphosphate Receptor 3) in Vascular Endothelium via KLF4 (Krüppel-Like Factor 4)-Mediated Histone Modifications.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
41 authors at 8 institutions in 3 countries.
Funding
Abstract
Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells.
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.