Oxidized low-density lipoproteins stimulate extracellular matrix metalloproteinase Inducer (EMMPRIN) release by

Cornelia Haug1, Christina Lenz, Fredy Díaz

  • 1Central Department Clinical Chemistry, University Hospital Ulm, Robert-Koch-Strasse 8, D-89070 Ulm, Germany. cornelia.haug@medizin.uni-ulm.de.

Abstract

Insights

Oxidized LDLs increase soluble EMMPRIN release from smooth muscle cells, promoting matrix degradation. This suggests a cycle where oxidized LDLs drive matrix metalloproteinase (MMP) release and activity in atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Cellular Biochemistry

Background:

  • Matrix metalloproteinases (MMPs) are implicated in atherogenesis.
  • Extracellular MMP inducer (EMMPRIN) stimulates MMP synthesis and is found in human atheroma.

Purpose of the Study:

  • To investigate the effect of oxidized low-density lipoproteins (oxLDLs) on EMMPRIN expression in human coronary artery smooth muscle cells (HCA-SMCs).

Main Methods:

  • HCA-SMCs were treated with oxLDLs.
  • EMMPRIN release and cell-associated levels were measured.
  • Western blot analysis was used to assess MMP-1 and MMP-2.
  • Effects of antioxidants, EDTA, and GM6001 were evaluated.

Main Results:

  • OxLDLs significantly increased EMMPRIN release into supernatants and decreased cell-associated EMMPRIN.
  • Antioxidants, EDTA, and GM6001 antagonized these oxLDL effects.
  • MMP-1 and MMP-2 induced shedding of EMMPRIN, and oxLDL upregulated MMP-1 and MMP-2 synthesis.
  • Soluble EMMPRIN from macrophages also increased MMP-1 and MMP-2 synthesis in HCA-SMCs.

Conclusions:

  • OxLDLs stimulate soluble EMMPRIN release via MMP-dependent shedding.
  • This process may create a feedback loop, as soluble EMMPRIN enhances MMP synthesis, contributing to matrix degradation in atherosclerosis.

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