title: Oxidized low-density lipoprotein-induced CD147 expression and its inhibition by high-density lipoprotein on platelets in vitro.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are believed to progressively degrade the collagenous components of the protective fibrous cap, leading to atherosclerotic plaque rupture or destabilization. Oxidized low-density lipoprotein (ox-LDL) enhances the release of CD147, known as the extracellular MMP inducer, from coronary smooth muscle cells. However, whether ox-LDL can induce platelet CD147 expression is unknown. Therefore, we investigated the influence of ox-LDL and high-density lipoprotein (HDL) on CD147 expression on human platelets.
  
  
  METHODS
  Washed platelets were incubated with ox-LDL (or native LDL) and HDL or anti-LOX-1 monoclonal antibody prior to incubation with ox-LDL. In parallel, buffer (PBS) was added to washed platelets as a control. The expression levels of CD147, CD62P, CD63 and Annexin V were assessed by flow cytometry, and soluble CD147 from the platelets was assessed by an enzyme-linked immunosorbent assay. Laser scanning microscopy (LSM) and transmission electron microscopy (TEM) were used to visualize the morphological changes and granule release, respectively, from the platelets.
  
  
  RESULTS
  Platelets treated with ox-LDL exhibited a significant increase in the expression of CD147 (or Annexin V), followed by increases in CD62P and CD63, compared with the control group. In contrast, HDL or anti-LOX-1 monoclonal antibody decreased these effects. The expression of soluble CD147 increased as the concentration of ox-LDL used to treat the platelets increased. After exposure to ox-LDL, morphological changes and granule release in the platelets were visualized by LSM and TEM. Additionally, the TEM revealed that HDL inhibits alpha-granule release.
  
  
  CONCLUSIONS
  In platelets, ox-LDL stimulates the release of CD147 via binding to LOX-1, whereas HDL inhibits this effect. This finding could provide new insights concerning the influence of ox-LDL and HDL on plaque stability by the up-regulation of CD147 on platelets.
authors.affiliation: Coronary Heart Disease Diagnosis and Treatment Center of the Chinese People's Liberation Army, the 305th Hospital of Chinese People's Liberation Army, Wenjin Street, Beijing, 100017, PR China.
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Yang
authors.forename: Yun-Tian
authors.initials: YT
authors.lastname: Li
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Du
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D051926:Basigin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood*; D006801:Humans; D008075:Lipoproteins, HDL / Q000276:immunology; D008077:Lipoproteins, LDL / Q000097:blood* / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D012016:Reference Values; D051127:Scavenger Receptors, Class E / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C497886:BSG protein, human; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D051926:Basigin; D020781:Matrix Metalloproteinase 1
keywords: ACS; CAD; CD147; ECM; EMMPRIN; HDL; MMPs; OCS; Ox-LDL; PRP; Plaque; Platelet; acute coronary syndromes; coronary artery disease; extracellular matrix; extracellular matrix metalloproteinase inducer; high-density lipoprotein; matrix metalloproteinases; open canalicular system; ox-LDL; oxidized low-density lipoprotein; platelet-rich plasma