title: Salvianolic acid A promotes the acceleration of neovascularization in the ischemic rat myocardium and the functions of endothelial progenitor cells.
abstract: BACKGROUND
  Salvia miltiorrhiza (SM, also known as DanShen) is one of the well-known widely used Chinese herbal medicines in clinical, containing phenolic compounds and potent antioxidant properties. Salvianolic acid A (SAA) is the most potent component of SM. A modern experimental strategy for treating myocardial ischemia is to induce neovascularization of the heart by the use of "angiogens", mediators that induce the formation of blood vessels, or angiogenesis. Studies demonstrated that coronary collateral vessels protect ischemic myocardium after coronary obstruction; therefore, we sought to examine whether SAA could stimulate myocardial angiogenesis.
  
  
  METHODS
  Male Sprague-Dawley rats myocardial infarct (MI) induced by ligation of left anterior descending coronary artery (LAD) were randomly divided into five groups: sham-operated group; LAD occlusion + administration of physiological saline (vehicle treated group); LAD occlusion + administration of different concentrations of SAA (10, 5.0 and 2.5mg/kg/d). Infarct size and capillary density in the infarct region were measured with a previous experimental method. Immunohistological analysis was performed to measure vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) expressions. The secretion of matrix metalloproteinase type X (MMP-9) was evaluated in serum of post-ischemic rats. We also performed the experiments of SAA on rat endothelial progenitor cells (EPCs) numbers and the capacity of migration and vasculargenesis.
  
  
  RESULTS
  SAA potentiated the ischemia-induced neovascularization after 1week post-operation when compared to vehicle treated group. This effect could be attributed to an increased formation of VEGF, VEGFR-2, and MMP-9 as well as the promotion of numbers and functions of EPCs.
  
  
  CONCLUSIONS
  These findings show that SAA has potent proangiogenic properties by promoting the expression of proangiogenic factors, and the functions of EPCs, indicating that SAA might contribute to the protective effect against coronary disease. Chemical compound studied in this paper is salvianolic acid A (PubChem CID: 5281793).
authors.affiliation: Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: lyjdcl@163.com.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Research and Development Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Chang-Ling
authors.initials: CL
authors.lastname: Duan
authors.affiliation: Research and Development Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. Electronic address: liujx0324@sina.com.
authors.forename: Jian-Xun
authors.initials: JX
authors.lastname: Liu
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D054443:Cell Migration Assays; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D007773:Lactates / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: D002109:Caffeic Acids; D016207:Cytokines; D007773:Lactates; C066201:salvianolic acid A
keywords: Coronary disease; Endothelial progenitor cells; Myocardial ischemia; Salvianolic acid A