Chang-Ling Li1, Bin Liu2, Zhao-Yang Wang2, Fei Xie2, Wen Qiao2, Jie Cheng2, Jiang-Ying Kuang3, Ying Wang2, Ming-Xiang Zhang4, De-Shan Liu5. 1. Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. 2. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. 3. Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, China. 4. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. Electronic address: zhangmingxiang@sdu.edu.cn. 5. Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China. Electronic address: liudeshan@sdu.edu.cn.
Abstract
BACKGROUND: Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear. METHODS: Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B. RESULTS: Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia. CONCLUSIONS: Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.
BACKGROUND:Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear. METHODS: Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B. RESULTS:Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia. CONCLUSIONS:Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.
Authors: Danfu Ma; Ahmed S Mandour; Ahmed Elfadadny; Hanan Hendawy; Tomohiko Yoshida; Hussein M El-Husseiny; Koji Nishifuji; Ken Takahashi; Zhenlei Zhou; Yanbing Zhao; Ryou Tanaka Journal: Front Vet Sci Date: 2022-06-16
Authors: Ele Ferrannini; Maria Laura Manca; Giulia Ferrannini; Felicita Andreotti; Daniele Andreini; Roberto Latini; Marco Magnoni; Stephen A Williams; Attilio Maseri; Aldo P Maggioni Journal: Front Cardiovasc Med Date: 2022-02-04