Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

Mol Imaging Biol. 2016 Apr;18(2):283-91. doi: 10.1007/s11307-015-0882-0.

Abstract

Purpose: In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated.

Procedures: Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense™ 680 and imaged with IVIS® Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages.

Results: There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and αSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages.

Conclusion: MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages.

Keywords: Atherosclerotic plaque; MMPSense; Macrophage; Matrix metalloproteinase; Smooth muscle cell.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carotid Stenosis / enzymology*
  • Carotid Stenosis / pathology
  • Demography
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescence
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Macrophages / enzymology*
  • Macrophages / pathology
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Myocytes, Smooth Muscle / enzymology*
  • Myocytes, Smooth Muscle / pathology
  • Plaque, Atherosclerotic / enzymology*
  • Plaque, Atherosclerotic / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Risk Factors

Substances

  • RNA, Messenger
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9