Oxidized low-density lipoprotein-induced CD147 expression and its inhibition by high-density lipoprotein on platelets in vitro

Abstract

Introduction: 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.

Materials and 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.

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.