دورية أكاديمية
Oxytocin Attenuates Sympathetic Innervation with Inhibition of Cardiac Mast Cell Degranulation in Rats after Myocardial Infarction.
| العنوان: | Oxytocin Attenuates Sympathetic Innervation with Inhibition of Cardiac Mast Cell Degranulation in Rats after Myocardial Infarction. |
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| المؤلفون: | Yin J; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Wang Y; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Han W; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Ge W; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Yu Q; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Jing Y; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Yan W; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Liu Q; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Gong L; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Yan S; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Wang S; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Li X; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Li Y; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.)., Hu H; Department of Cardiology (J.Y., Y.W., S.Y., H.H.), Department of Emergency Medicine (X.L.), and Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine (Y.L.), The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, China; Department of Cardiology, Shandong Provincial Hospital affiliated with Shandong First Medical University, Jinan, China (J.Y., W.H.); Department of Cardiology, Taizhou Hospital of Zhejiang Province affiliated with Wenzhou Medical University, Zhejiang, China (W.G.); School of Medicine, Shandong University, Jinan, China (Q.Y., Y.J., W.Y., Q.L.); Department of Infectious Disease and Hepatology, the Second Hospital of Shandong University, Shandong University, Jinan, China (L.G.); and Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China (S.W.) huhesheng@sfdmu.edu.cn liyanhbs@163.com. |
| المصدر: | The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2024 Jul 18; Vol. 390 (2), pp. 240-249. Date of Electronic Publication: 2024 Jul 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 0376362 Publication Model: Electronic Cited Medium: Internet ISSN: 1521-0103 (Electronic) Linking ISSN: 00223565 NLM ISO Abbreviation: J Pharmacol Exp Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Bethesda, MD : American Society for Pharmacology and Experimental Therapeutics Original Publication: Baltimore : Williams & Wilkins |
| مواضيع طبية MeSH: | Oxytocin*/pharmacology , Oxytocin*/metabolism , Myocardial Infarction*/drug therapy , Myocardial Infarction*/metabolism , Mast Cells*/drug effects , Mast Cells*/metabolism , Sympathetic Nervous System*/drug effects , Sympathetic Nervous System*/metabolism , Cell Degranulation*/drug effects , Receptors, Oxytocin*/metabolism , Receptors, Oxytocin*/antagonists & inhibitors , Rats, Sprague-Dawley*, Animals ; Rats ; Male ; Mice ; Signal Transduction/drug effects ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Arrhythmias, Cardiac/metabolism ; Arrhythmias, Cardiac/drug therapy ; Arrhythmias, Cardiac/etiology |
| مستخلص: | Sympathetic hyperinnervation is the leading cause of fatal ventricular arrhythmia (VA) after myocardial infarction (MI). Cardiac mast cells cause arrhythmias directly through degranulation. However, the role and mechanism of mast cell degranulation in sympathetic remodeling remain unknown. We investigated the role of oxytocin (OT) in stabilizing cardiac mast cells and improving sympathetic innervation in rats. MI was induced by coronary artery ligation. Western blotting, immunofluorescence, and toluidine staining of mast cells were performed to determine the expression and location of target protein. Mast cells accumulated significantly in peri-infarcted tissues and were present in a degranulated state. They expressed OT receptor (OTR), and OT infusion reduced the number of degranulated cardiac mast cells post-MI. Sympathetic hyperinnervation was attenuated as assessed by immunofluorescence for tyrosine hydroxylase (TH). Seven days post-MI, the arrhythmia score of programmed electrical stimulation was higher in vehicle-treated rats with MI than in rats treated with OT. An in vitro study showed that OT stabilized mast cells via the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Further in vivo studies on OTR-deficient mice showed worsening mast cell degranulation and worsening sympathetic innervation. OT pretreatment inhibited cardiac mast cell degranulation post-MI and prevented sympathetic hyperinnervation, along with mast cell stabilization via the PI3K/Akt pathway. SIGNIFICANCE STATEMENT: This is the first study to elucidate the role and mechanism of oxytocin (OT) in inflammatory-sympathetic communication mediated sympathetic hyperinnervation after myocardial infarction (MI), providing new approaches to prevent fatal arrhythmias. (Copyright © 2024 by The Author(s).) |
| المشرفين على المادة: | 50-56-6 (Oxytocin) 0 (Receptors, Oxytocin) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
| تواريخ الأحداث: | Date Created: 20240620 Date Completed: 20240718 Latest Revision: 20240718 |
| رمز التحديث: | 20240719 |
| DOI: | 10.1124/jpet.124.002064 |
| PMID: | 38902033 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1521-0103 |
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| DOI: | 10.1124/jpet.124.002064 |