ArticleCirculation2015
Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a.
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Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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96citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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Who cites it
96 citing papers in PubMed, 154 citations in OpenAlex.
- miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease.Circulation research · 2017Trial
- Transcriptomic Profiling Identifies Disease-Specific miRNA-mRNA Regulatory Networks in Systemic Sclerosis.Biomolecules · 2026Article
- SREBP2 promotes macrophage alternative activation and allergic airway inflammation independent of cholesterol biosynthesis.Cell death & disease · 2026Article
- Review
- Transient miR-92a Induction in Intermediate Monocytes (CD14International journal of molecular sciences · 2026Article
- The Role of Immune Infiltration and Oxidative Stress in the Progression of Cerebral Cavernous Malformation.Brain and behavior · 2026Review
- miR-92a aggravates metabolic syndrome via KLF2/miR-483 axis.Journal of diabetes investigation · 2025Article
- Cellular Phenotypic Transformation During Atherosclerosis: The Potential Role of miRNAs as Biomarkers.International journal of molecular sciences · 2025Review
- Emerging Gene Therapy Based on Nanocarriers: A Promising Therapeutic Alternative for Cardiovascular Diseases and a Novel Strategy in Valvular Heart Disease.International journal of molecular sciences · 2025Review
- Hesperidin alleviates hypothyroidism-related cardiac dysfunction by targeting cardiac miRNAs, Nrf2/NF-κB signaling, oxidative stress and inflammation.Frontiers in pharmacology · 2025Article
- Mitigating Vascular Inflammation by Mimicking AIBP Mechanisms: A New Therapeutic End for Atherosclerotic Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Unraveling the miRNA Puzzle in Atherosclerosis: Revolutionizing Diagnosis, Prognosis, and Therapeutic Approaches.Current atherosclerosis reports · 2024Review
- LncRNA GAS5 restrains ISO-induced cardiac fibrosis by modulating mir-217 regulation of SIRT1.Scientific reports · 2024Article
- Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines.Frontiers in pharmacology · 2024Article
- Vascular mechanotransduction.Physiological reviews · 2023Review
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
- Obstructive Sleep Apnea-induced Endothelial Dysfunction Is Mediated by miR-210.American journal of respiratory and critical care medicine · 2023Article
- MiR-92a expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening.American journal of translational research · 2023Article
- Hypercapnia increases ACE2 expression and pseudo-SARS-CoV-2 entry in bronchial epithelial cells by augmenting cellular cholesterol.Frontiers in immunology · 2023Article
- microRNAs Associated with Carotid Plaque Development and Vulnerability: The Clinician's Perspective.International journal of molecular sciences · 2022Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 3 countries.
Zhen ChenFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.). jshyy@ucsd.edu zchen@ucsd.edu.
Liang WenFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Marcy MartinFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Chien-Yi HsuFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Longhou FangFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Feng-Mao LinFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Ting-Yang LinFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
McKenna J GearyFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Greg G GearyFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Yongli ZhaoFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
David A JohnsonFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Jaw-Wen ChenFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Shing-Jong LinFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Shu ChienFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Hsien-Da HuangFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Yury I MillerFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
Po-Hsun HuangFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.).
John Y-J ShyyFrom Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan (C.-Y.H., J.-W.C., S.-J.L., P.-H.H.); Institute of Bioinformatics and Systems Biology and Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan (F.-M.L., H.-D.H.); Department of Kinesiology and Health Sciences, California State University, San Bernardino (G.G.); and Cardiovascular Research Center, Medical School, Xi'an Jiaotong University, Xi'an, China (Y.Z., J.Y.-J.S.). jshyy@ucsd.edu zchen@ucsd.edu.
University of California, Riverside · USHouston Methodist · US
Funding
Systems Biology Analyses for Hemodynamic Regulation of Vascular HomeostasisR01HL108735 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2012 to 2024
$13.4MTraining In Cardiovascular Physiology & PharmacologyT32HL007444 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Ju Chen, Robert Scott Ross · 1985 to 2026
$11.1MShear Regulation of MicroRNA Transportomes and Targetomes in Vascular HomeostasisR01HL106579 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2011 to 2022
$8.3MZebrafish models of vascular inflammation and atherosclerosisR01HL093767 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY · 2009 to 2014
$2.5MShear Stress, AMPK, and Endothelial FunctionsR01HL089940 · NHLBI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SHYY, JOHN YJ · 2009 to 2013
$1.9MShear stress, SIRT1, and Arterial StiffeningR01HL105318 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHYY, JOHN YJ · 2010 to 2013
$1.5MFlow Regulation of SREBP in AtherosclerosisR01HL077448 · NHLBI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SHYY, JOHN Y-J Y-J · 2004 to 2007
$1.4MHypoxia-Suppressed Dicer and AGO1 Promote AngiogenesisK99HL122368 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, ZHEN BOUMAN · 2014 to 2015
$268kNHLBI NIH HHS K99 HL122368NHLBI NIH HHS K99HL122368NHLBI NIH HHS R01 HL077448NHLBI NIH HHS R01 HL089940NHLBI NIH HHS R01 HL093767NHLBI NIH HHS R01HL093767NHLBI NIH HHS R01 HL105318NHLBI NIH HHS R01HL105318NHLBI NIH HHS R01 HL106579NHLBI NIH HHS R01HL106579NHLBI NIH HHS R01 HL108735NHLBI NIH HHS R01HL108735NHLBI NIH HHS R01HL89940NHLBI NIH HHS T32 HL007444
Abstract
backgroundOxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase-derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element-binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium. METHODS AND
resultsUsing cultured endothelial cells challenged by diverse oxidative stresses, hypercholesterolemic zebrafish, and angiotensin II-infused or aged mice, we demonstrated that SREBP2 transactivation of microRNA-92a (miR-92a) is oxidative stress inducible. The SREBP2-induced miR-92a targets key molecules in endothelial homeostasis, including sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4, leading to NOD-like receptor family pyrin domain-containing 3 inflammasome activation and endothelial nitric oxide synthase inhibition. In endothelial cell-specific SREBP2 transgenic mice, locked nucleic acid-modified antisense miR-92a attenuates inflammasome, improves vasodilation, and ameliorates angiotensin II-induced and aging-related atherogenesis. In patients with coronary artery disease, the level of circulating miR-92a is inversely correlated with endothelial cell-dependent, flow-mediated vasodilation and is positively correlated with serum level of interleukin-1β.
conclusionsOur findings suggest that SREBP2-miR-92a-inflammasome exacerbates endothelial dysfunction during oxidative stress. Identification of this mechanism may help in the diagnosis or treatment of disorders associated with oxidative stress, innate immune activation, and endothelial dysfunction.
Indexed as
Transcriptional ActivationAgedAngiotensin IIAnimalsCoronary DiseaseEndothelial CellsEndothelium, VascularFemaleFree Radical ScavengersGene Expression RegulationGenes, ReporterHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsHydrogen PeroxideHypercholesterolemiaAngiotensin IIEUK-134Free Radical ScavengersHydrogen PeroxideInflammasomesInterleukin-1betaKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Lipoproteins, LDLMicroRNAsMIRN92 microRNA, humanMirn92 microRNA, mouseMIRN92 microRNA, zebrafishOrganometallic Compoundsoxidized low density lipoproteinRecombinant Fusion ProteinsSalicylatesSterol Regulatory Element Binding Protein 2Zebrafish ProteinsendotheliuminflammasomesmicroRNA-92oxidative stresssterol regulatory element binding protein 2
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