ArticleCirculation2017
Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility.
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Article in Circulation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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71citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
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Who cites it
71 citing papers in PubMed, 119 citations in OpenAlex.
- Human Plasma Metabolomics Implicates Modified 9-cis-Retinoic Acid in the Phenotype of Left Main Artery Lesions in Acute ST-Segment Elevated Myocardial Infarction.Scientific reports · 2018Trial
- Liraglutide ameliorates obese type 2 diabetes by regulating macrophage cholesterol metabolism and H3K27ac modification to promote M2 polarization and adipocyte thermogenic activation.Journal of molecular histology · 2026Article
- Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow.Journal of proteome research · 2026Article
- Macrophage membrane-functionalized biomimetic Yiqi Huoxue formula nanoparticles improve atherosclerosis by regulating smooth muscle cell phenotypic transition via the KLF4/NF-κB pathway.Chinese medicine · 2026Article
- Acute mitochondrial dysfunction impairs neuromuscular transmission and contractility in mouse diaphragm: the protective potential of 25-hydroxycholesterol.Journal of physiology and biochemistry · 2026Article
- Non-canonical ceRNA-independent mechanism of the lncRNA-H19/miR-212-5p axis targeting KLF4 in Hcy-triggered VSMCs dysfunction and atherogenesis.Scientific reports · 2026Article
- Decoding the Kruppel-like Transcription Factors in Atherosclerosis: Insight from Molecular and Translational Perspectives.International journal of molecular sciences · 2025Review
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- A Novel Function of NaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- SilencingInternational journal of molecular sciences · 2025Article
- Exploring the Roles of Liver X Receptors in Lipid Metabolism and Immunity in Atherosclerosis.Biomolecules · 2025Review
- 25-Hydroxycholesterol as a negative regulator of diaphragm muscle contractions via estrogen receptor and CaHistochemistry and cell biology · 2025Article
- Implications of Krüppel-like factor signaling in neuroinflammation for neurodegenerative diseases.American journal of translational research · 2025Review
- Functional omics of ORP7 in primary endothelial cells.BMC biology · 2024Article
- MicroRNA Inhibiting Atheroprotective Proteins in Patients with Unstable Angina Comparing to Chronic Coronary Syndrome.International journal of molecular sciences · 2024Article
- Epsins oversee smooth muscle cell reprograming by influencing master regulators KLF4 and OCT4.bioRxiv : the preprint server for biology · 2024Article
- Cholesterol 25-Hydroxylase Protects Against Diabetic Kidney Disease by Regulating ADP Ribosylation Factor 4.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Macrophage polarisation and inflammatory mechanisms in atherosclerosis: Implications for prevention and treatment.Heliyon · 2024Review
- Molecular mechanism of renal lipid accumulation in diabetic kidney disease.Journal of cellular and molecular medicine · 2024Review
- Pathogenic mycobacterium upregulates cholesterol 25-hydroxylase to promote granuloma development via foam cell formation.iScience · 2024Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 1 institution in 3 countries.
Zhao LiFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Marcy MartinFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Jin ZhangFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Hsi-Yuan HuangFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Liang BaiFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Jiao ZhangFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Jian KangFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Ming HeFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Jie LiFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Mano R MauryaFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Shakti GuptaFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Guangjin ZhouFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Panjamaporn SangwungFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Yong-Jiang XuFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Ting LeiFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Hsien-Da HuangFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Mohit JainFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Mukesh K JainFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
Shankar SubramaniamFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.).
John Y-J ShyyFrom Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (M.M., Jin Zhang, J.K., M.H., Y.-J.X., M.J., J.Y.-J.S.);Department of Bioengineering, University of California, San Diego, La Jolla (M.R.M., S.G.); Division of Biochemistry and Molecular Biology, University of California, Riverside (M.M.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (H.-Y.H., H.-D.H.); and Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (G.Z., P.S., M.K.J.). jshyy@ucsd.edu.
University of California, Riverside · US
Funding
Training In Cardiovascular Physiology & PharmacologyT32HL007444 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Ju Chen, Robert Scott Ross · 1985 to 2026
$11.1MMapping the Plasma Exposome and its Association with Human Cardiovascular DiseaseR01ES027595 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAIN, MOHIT · 2017 to 2021
$3.3MFlow-Induced Endothelial Innate Immunity and Atherosclerosis SusceptibilityR01HL125643 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHYY, JOHN YJ · 2016 to 2019
$1.7MShear stress, SIRT1, and Arterial StiffeningR01HL105318 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHYY, JOHN YJ · 2010 to 2013
$1.5MRapidFire mass spectrometry systemS10OD020025 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAIN, MOHIT · 2015 to 2015
$600kNHLBI NIH HHS R01 HL105318NHLBI NIH HHS R01 HL125643NHLBI NIH HHS T32 HL007444NIEHS NIH HHS R01 ES027595NIH HHS S10 OD020025
Abstract
backgroundAtherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall (eg, endothelial cells [ECs]), as well as circulating and resident immunogenic cells (eg, monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of SREBP2 (sterol regulatory element-binding protein 2), 25-hydroxycholesterol, and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages.
methodsBioinformatic analyses were used to investigate RNA-sequencing data to identify cholesterol oxidation and efflux genes regulated by Krüppel-like factor 4 (KLF4). In vitro experiments involving cultured ECs and macrophages and in vivo methods involving mice with Ch25h ablation were then used to explore the atheroprotective role of KLF4-Ch25h/LXR.
resultsVasoprotective stimuli increased the expression of Ch25h and LXR via KLF4. The KLF4-Ch25h/LXR homeostatic axis functions through suppressing inflammation, evidenced by the reduction of inflammasome activity in ECs and the promotion of M1 to M2 phenotypic transition in macrophages. The increased atherosclerosis in apolipoprotein E
conclusionsKLF4 transactivates Ch25h and LXR, thereby promoting the synergistic effects between ECs and macrophages to protect against atherosclerosis susceptibility.
Indexed as
AnimalsAtherosclerosisGene ExpressionHumansHydroxycholesterolsKruppel-Like Factor 4Kruppel-Like Transcription FactorsLiver X ReceptorsMaleMice25-hydroxycholesterolHydroxycholesterolsKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsLiver X Receptorsatherosclerosischolesterolendothelial cellsinflammationmacrophagesshear stress
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