ArticleCirculation2016
Critical Roles of STAT3 in β-Adrenergic Functions in the Heart.
Abstract read
In one paragraph
Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% of its field
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review.Journal of experimental & clinical cancer research : CR · 2019Pooled it
- Sam68 Exacerbates Pathologic Cardiac Hypertrophy by Suppressing Cardiomyocyte Glucose Oxidation.Circulation · 2026Article
- β-Adrenergic receptors as immunomodulators in T cells: mechanisms of neuroimmune crosstalk and pathophysiological implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Transcriptional regulatory network analysis uncovers modular gene control and potential key regulators in diabetic cardiomyopathy.Frontiers in cell and developmental biology · 2026Article
- Cardiomyocyte Janus kinase 1 (JAK1) signaling is required for cardiac homeostasis and cytokine-dependent activation of STAT3.Journal of molecular and cellular cardiology · 2025Article
- TSH upregulates CYP4B1 through the PI3K/AKT/CREB pathway to promote cardiac hypertrophy.Journal of endocrinological investigation · 2025Article
- AAV viral vectors as therapeutic interventions for inherited or non-inherited cardiac disorders: current aspects and future prospects.Frontiers in medicine · 2025Review
- Heart failure, inflammation and exercise.International journal of biological sciences · 2025Review
- The functional role of m6A demethylase ALKBH5 in cardiomyocyte hypertrophy.Cell death & disease · 2024Article
- STAT protein family and cardiovascular diseases: overview of pathological mechanisms and therapeutic implications.Molecular biology reports · 2024Review
- JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target.Frontiers in pharmacology · 2024Review
- Article
- PTX3 from vascular endothelial cells contributes to trastuzumab-induced cardiac complications.Cardiovascular research · 2023Article
- Intralipid® improves left ventricular function in rats with lipopolysaccharide-induced endotoxaemia by a Src-STAT3-mediated mechanism.British journal of anaesthesia · 2023Article
- Lotus Bee Pollen Extract Inhibits Isoproterenol-Induced Hypertrophy via JAK2/STAT3 Signaling Pathway in Rat H9c2 Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Aging-Induced Impairment of Vascular Function: Mitochondrial Redox Contributions and Physiological/Clinical Implications.Antioxidants & redox signaling · 2021Review
- Regulation of STAT3 and its role in cardioprotection by conditioning: focus on non-genomic roles targeting mitochondrial function.Basic research in cardiology · 2021Review
- Sorting nexin 3 induces heart failure via promoting retromer-dependent nuclear trafficking of STAT3.Cell death and differentiation · 2021Article
- Differences in molecular phenotype in mouse and human hypertrophic cardiomyopathy.Scientific reports · 2021Article
- Src-family Protein Tyrosine Kinases: A promising target for treating Cardiovascular Diseases.International journal of medical sciences · 2021Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Wenjun ZhangFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.). wenjun08@gmail.com wenzhang@iu.edu wnshou@gmail.com wshou@iu.edu.
Xiuxia QuFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Biyi ChenFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Marylynn SnyderFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Meijing WangFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Baiyan LiFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Yue TangFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Hanying ChenFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Wuqiang ZhuFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Li ZhanFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Ni YinFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Deqiang LiFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Li XieFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Ying LiuFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
J Jillian ZhangFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Xin-Yuan FuFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Michael RubartFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Long-Sheng SongFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Xin-Yun HuangFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.).
Weinian ShouFrom State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (W. Zhang, X.Q., Y.T., W.S.); Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indianapolis, IN (W. Zhang, B.L., H.C., W. Zhu, L.Z., N.Y., D.L., L.X., Y.L., M.R., W.S.); Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City (B.C., L.-S.S.); Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, NY (M.S., J.J.Z., X.-Y.H.); Department of Surgery, Indiana University School of Medicine, Indianapolis (M.W.); Department of Pharmacology, Harbin Medical University, Harbin, China (B.L.); Department of Heart Surgery, Xiangya 2nd Hospital, Central South University, Changsha, China (N.Y., L.X.); and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis (X.-Y.F.). wenjun08@gmail.com wenzhang@iu.edu wnshou@gmail.com wshou@iu.edu.
Central South University · CNCornell University · USUniversity of Iowa · USIndiana University School of MedicineXiangya Hospital Central South University · CNHarbin Medical University · CNIndiana University – Purdue University Indianapolis · US
Funding
Novel Functions of the E-C Coupling Structural Protein Junctophilin-2 in the HeartR01HL130346 · NHLBI · UNIVERSITY OF IOWA · PI SONG, LONG-SHENG · 2016 to 2023
$4.4MT-tubule remodeling and Ca2+-dependent arrhythmogenesis in cardiomyopathies.R01HL090905 · NHLBI · UNIVERSITY OF IOWA · PI SONG, LONG-SHENG · 2008 to 2017
$4.0MSignaling Mechanisms of Heterotrimeric G proteinsR01HL091525 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI HUANG, XIN-YUN · 2008 to 2012
$2.1MMolecular Pathway in Myocardium DevelopmentR01HL081092 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SHOU, WEINIAN · 2007 to 2011
$1.9MRoles of STAT proteins in tumor vaccine developmentR01CA125568 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI FU, XIN-YUAN · 2007 to 2011
$1.4MBehavioral Characteristics and Neural Correlates of Reading Impairment in FASDU01AA023503 · NIAAA · WAYNE STATE UNIVERSITY · PI GAAB, NADINE, JACOBSON, SANDRA W. · 2015 to 2017
$980kBehavioral Characteristics and Neural Correlates of Reading Impairment in FASDR01AA023503 · NIAAA · WAYNE STATE UNIVERSITY · PI GAAB, NADINE, JACOBSON, SANDRA W. · 2018 to 2019
$640kNCI NIH HHS CA125568-05NCI NIH HHS R01 CA125568NHLBI NIH HHS HL090905NHLBI NIH HHS HL81092NHLBI NIH HHS HL91525NHLBI NIH HHS R01 HL081092NHLBI NIH HHS R01 HL090905NHLBI NIH HHS R01 HL091525NHLBI NIH HHS R01 HL130346NIAAA NIH HHS R01 AA023503NIAAA NIH HHS U01 AA023503
Abstract
backgroundβ-Adrenergic receptors (βARs) play paradoxical roles in the heart. On one hand, βARs augment cardiac performance to fulfill the physiological demands, but on the other hand, prolonged activations of βARs exert deleterious effects that result in heart failure. The signal transducer and activator of transcription 3 (STAT3) plays a dynamic role in integrating multiple cytokine signaling pathways in a number of tissues. Altered activation of STAT3 has been observed in failing hearts in both human patients and animal models. Our objective is to determine the potential regulatory roles of STAT3 in cardiac βAR-mediated signaling and function. METHODS AND
resultsWe observed that STAT3 can be directly activated in cardiomyocytes by β-adrenergic agonists. To follow up this finding, we analyzed βAR function in cardiomyocyte-restricted STAT3 knockouts and discovered that the conditional loss of STAT3 in cardiomyocytes markedly reduced the cardiac contractile response to acute βAR stimulation, and caused disengagement of calcium coupling and muscle contraction. Under chronic β-adrenergic stimulation, Stat3cKO hearts exhibited pronounced cardiomyocyte hypertrophy, cell death, and subsequent cardiac fibrosis. Biochemical and genetic data supported that Gαs and Src kinases are required for βAR-mediated activation of STAT3. Finally, we demonstrated that STAT3 transcriptionally regulates several key components of βAR pathway, including β1AR, protein kinase A, and T-type Ca(2+) channels.
conclusionsOur data demonstrate for the first time that STAT3 has a fundamental role in βAR signaling and functions in the heart. STAT3 serves as a critical transcriptional regulator for βAR-mediated cardiac stress adaption, pathological remodeling, and heart failure.
Indexed as
Adrenergic beta-AgonistsAnimalsCell LineHeartMaleMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacOrgan Culture TechniquesReceptors, Adrenergic, betaSTAT3 Transcription FactorAdrenergic beta-AgonistsReceptors, Adrenergic, betaStat3 protein, mouseSTAT3 Transcription Factorheart failurereceptors, adrenergicreceptors, G-protein-coupledSTAT3 transcription factor
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