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MMP-2 and MMP-9 are prominent matrix metalloproteinases during atherosclerosis development in the

Dick Wågsäter1, Chaoyong Zhu, Johan Björkegren

  • 1Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Solna, Stockholm, Sweden. dick.wagsater@ki.se

International Journal of Molecular Medicine
|May 14, 2011
PubMed

Insights

Matrix-degrading proteases like matrix metalloproteinases (MMPs) are crucial in atherosclerosis. This study found MMP-2 and MMP-9 expression increased in advanced lesions, suggesting their key role in disease progression.

Area of Science:

  • Cardiovascular Biology
  • Protease Biochemistry
  • Atherosclerosis Research

Background:

  • Extracellular matrix-degrading proteases influence atherosclerotic lesion development.
  • Understanding matrix metalloproteinase (MMP) roles is vital for atherosclerosis research.

Purpose of the Study:

  • To investigate matrix metalloproteinase (MMP) expression during early atherosclerosis in a relevant mouse model.
  • To identify specific MMPs involved in the progression of atherosclerotic lesions.

Main Methods:

  • Utilized Ldlr(-/-)Apob(100/100) mice, mimicking human lipoprotein profiles.
  • Analyzed expression of 11 proteases and 3 inhibitors across 5-40 weeks.
  • Employed real-time PCR, zymography, and immunohistochemistry to assess MMP activity and localization.

Main Results:

  • MMP-2 and MMP-9 expression and activity significantly increased in advanced atherosclerotic lesions with macrophage infiltration.
  • Expression of other MMPs did not consistently increase; MMP-8 and MMP-13 mRNA were downregulated.
  • Downregulation of MMP-8 and MMP-13 may correlate with higher collagen levels in vessels.

Conclusions:

  • Low proteolytic activity in early atherogenesis and a limited protease repertoire are linked to atherosclerosis progression in this model.
  • MMP-2 and MMP-9 are identified as the primary proteases driving atherogenesis in the Ldlr(-/-)Apob(100/100) mouse model.

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