title: Anti-fibrosis effect of scutellarin via inhibition of endothelial-mesenchymal transition on isoprenaline-induced myocardial fibrosis in rats.
abstract: Scutellarin (SCU) is the major active component of breviscapine and has been reported to be capable of decreasing myocardial fibrosis. The aim of the present study is to investigate whether SCU treatment attenuates isoprenaline-induced myocardial fibrosis and the mechanisms of its action. Rats were injected subcutaneously with isoprenaline (Iso) to induce myocardial fibrosis and rats in the SCU treatment groups were intraperitoneally infused with SCU (10 mg·kg-1·d-1 or 20 mg·kg-1·d-1, for 14 days). Post-treatment, cardiac functional measurements and the left and right ventricular weight indices (LVWI and RVWI, respectively) were analysed. Pathological alteration, expression of type I and III collagen, Von Willebrand factor, α-smooth muscle actin, cluster of differentiation-31 (CD31), and the Notch signalling proteins (Notch1, Jagged1 and Hes1) were examined. The administration of SCU resulted in a significant improvement in cardiac function and decrease in the cardiac weight indices; reduced fibrous tissue proliferation; reduced levels of type I and III collagen; increased microvascular density; and decreased expression of α-smooth muscle actin and increased expression of CD31, Notch1, Jagged1 and Hes1 in isoprenaline-induced myocardial fibrosis in rats. Our results suggest that SCU prevents isoprenaline-induced myocardial fibrosis via inhibition of cardiac endothelial-mesenchymal transition potentially, which may be associated with the Notch pathway.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. wyzh66@126.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Ningbo First Hospital, Ningbo 315000, China. cx6176@gmail.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Clinical LaboratoryDepartment, Wenzhou Central Hospital, Wenzhou 325000, China. clzwz@sina.com.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Coronary Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. zhouxihw@gmail.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. zhenggaoshu@163.com.
authors.forename: Gaoshu
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. wyzh66@126.com.
authors.forename: Huaiqin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. huangweijian@hosp1.ac.cn.
authors.forename: Weijian
authors.initials: W
authors.lastname: Huang
authors.affiliation: Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. cjj1959586233@126.com.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Cai
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D047310:Apigenin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005965:Glucuronates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000009:adverse effects; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D015394:Molecular Structure; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D051881:Receptor, Notch1 / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D000199:Actins; D047310:Apigenin; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D005965:Glucuronates; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C000606275:Jag1 protein, rat; C498862:Acta2 protein, rat; C484876:scutellarin