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MMP9 production by human monocyte-derived macrophages is decreased on polymerized type I collagen

S Lepidi1, R D Kenagy, E W Raines

  • 1Department of Surgery, University of Washington School of Medicine, Seattle, USA.

Journal of Vascular Surgery
|December 18, 2001
PubMed

Insights

Macrophages produce matrix metalloproteinases (MMPs), like MMP9, which can destabilize atherosclerotic plaques. Polymerized collagen matrix suppresses MMP9 production, but its disruption may increase MMP9, raising aneurysm rupture risk.

Area of Science:

  • Cardiovascular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Macrophage-derived matrix metalloproteinases (MMPs), particularly MMP9, are implicated in atherosclerotic plaque instability and aortic aneurysm rupture.
  • Understanding the regulation of MMP9 by the extracellular matrix and cytokines is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the role of the collagen matrix and soluble cytokines in regulating monocyte/macrophage MMP9 expression.
  • To determine how the physical state of collagen influences MMP9 synthesis.

Main Methods:

  • Monocytes were differentiated into macrophages on tissue-culture plastic, polymerized collagen, or monomer collagen.
  • Macrophage MMP9 synthesis was quantified under basal conditions and in response to stimulation with interleukin-1beta, tumor necrosis factor-alpha, and platelet-derived growth factor BB.
  • MMP9 production was compared between cells cultured on different substrates and in suspension.

Main Results:

  • Macrophages cultured on tissue-culture plastic produced maximal MMP9 and were unresponsive to cytokine stimulation.
  • Macrophages cultured on polymerized collagen synthesized significantly less MMP9 basally but showed increased responsiveness to cytokines.
  • Culturing monocytes in suspension followed by seeding on polymerized collagen decreased MMP9 synthesis, while monomer collagen showed a modest increase.

Conclusions:

  • Native, polymerized collagen matrix appears to negatively regulate macrophage MMP9 synthesis.
  • Disruption of the native collagen conformation may enhance MMP9 production, potentially increasing the risk of plaque rupture.
  • Macrophage interaction with the collagen matrix influences their responsiveness to soluble inflammatory mediators.

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