title: A polysaccharide, MDG-1, induces S1P1 and bFGF expression and augments survival and angiogenesis in the ischemic heart.
abstract: Ophiopogon japonicus is a traditional Chinese medicine used to treat cardiovascular disease. Recent studies have confirmed its beneficial properties, but not the mechanism of action. Herein, we investigate the anti-ischemic properties of a water-soluble beta-d-fructan (MDG-1) from Ophiopogon japonicus, and assess the cytoprotective and proangiogenic effects of MDG-1. MDG-1 protects cardiomyocyte and microvascular endothelial cells (HMEC-1) against oxygen glucose deprivation (OGD)-induced cell death, as well as protect myocardial cells from ischemia-induced death occurring after coronary artery ligation in rats. Meanwhile, MDG-1 stimulates the differentiation of HMEC-1 cells into capillary-like structures in vitro and functions as a chemoattractant in migration assays, and promotes neovascularization in ischemic myocardium. In addition, MDG-1 upregulates sphingosine kinase 1 and sphingosine-1-phosphate (S1P) receptor 1 expression. Both MDG-1 and S1P induce basic fibroblast growth factor (bFGF) expression in HMEC-1 cells. Further study revealed that both MDG-1 and S1P induce Akt and ERK phosphorylation in a dose- and time-dependent manner, an effect that is attenuated by pre-treatment with either the Akt inhibitor wortmannin or the ERK inhibitor PD98059, and MDG-1 can also induce eNOS phosphorylation and increases in production of NO. These data indicate that MDG-1 presented remarkable anti-ischemic activity and protects cardiomyocyte and HMEC-1 cells from ischemia-induced cell damage by inducing S1P1 and bFGF cytoprotective and proangiogenic effects via the S1P/bFGF/Akt/ERK/eNOS signaling pathway.
authors.affiliation: Engineering Research Center of Modern Preparation Technology of TCM, Shanghai University of Traditional Chinese Medicine, Pudong, Shanghai, 201203, People's Republic of China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.forename: Kan
authors.initials: K
authors.lastname: Ding
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D016222:Fibroblast Growth Factor 2; C060506:sphingosine 1-phosphate; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D013110:Sphingosine