title: Genistein suppresses smooth muscle cell-derived foam cell formation through tyrosine kinase pathway.
abstract: OBJECTIVE
  Genistein, as a protein tyrosine kinase inhibitor, has been shown to possess anti-atherosclerotic effects. Since the smooth muscle cell-derived foam cells are key components of atherosclerotic plaques. The aim of this study is to investigate the influence of genistein on foam cell transformation from vascular smooth muscle cells and possible mechanisms contributing to these effects.
  
  
  RESULTS
  Vascular smooth muscle cells exposed to ox-LDL developed into foam cell, as demonstrated by Oil Red O staining and cholesterol content analysis. Ox-LDL induced phenotype transformation of smooth muscle cells, decreased expression of α-actin and increased expression of CD68 (a specific marker for monocytes, can also function as a subtype of scavenger receptors). The expression of scavenger receptors CD36 and LOX-1 was measured, and their role in foam cell formation in the presence of genistein, daidzein (a structurally similar analogue of genistein) and herbimycin A (a commonly tyrosine kinase inhibitor). The results showed that foam cell formation was markedly reduced by genistein and herbimycin A, as well as the expression of CD68, CD36 and LOX-1. However, daidzein had no such effect. In addition, genistein-induced down-regulation of CD68, CD36 and LOX-1 could be reversed by sodium orthovanadate (a membrane-permeable protein tyrosine phosphatase inhibitor).
  
  
  CONCLUSIONS
  The results showed that ox-LDL induce smooth muscle cell-derived foam cell formation and transform the phenotype of smooth muscle cell. While tyrosine kinase inhibitor, genistein could suppress smooth muscle cell-derived foam cell formation through inhibiting the protein expressions of CD68, CD36 and LOX-1.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China.
authors.forename: Jinghan
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China.
authors.forename: Meimei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China.
authors.forename: Tingjiao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Post Street, Harbin 150001, PR China. Electronic address: zfx0001@126.com.
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019833:Genistein / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017828:Rifabutin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D007529:Isoflavones; D008077:Lipoproteins, LDL; D047428:Protein Kinase Inhibitors; C099252:oxidized low density lipoprotein; D017828:Rifabutin; C004742:daidzein; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases
keywords: CD36; CD68; Genistein; LOX-1; Smooth muscle cell-derived foam cells; Tyrosine kinase