Salvianolic acid B improves myocardial function in diabetic cardiomyopathy by suppressing IGFBP3.

Autor: Li CL; 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., Liu B; 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., Wang ZY; 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., Xie F; 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., Qiao W; 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., Cheng J; 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., Kuang JY; Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, China., Wang Y; 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., Zhang MX; 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., Liu DS; Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China. Electronic address: liudeshan@sdu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2020 Feb; Vol. 139, pp. 98-112. Date of Electronic Publication: 2020 Jan 23.
DOI: 10.1016/j.yjmcc.2020.01.009
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.yjmcc.2020.01.009.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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