Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques

Yoshihiro Fukumoto, Jun O. Deguchi, Peter Libby, Elena Rabkin-Aikawa, Yasuhiko Sakata, Michael T. Chin, Christopher C. Hill, Patrick R. Lawler, Nerea Varo, Frederick J. Schoen, Stephen M. Krane, Masanori Aikawa

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67 Citations (Scopus)

Abstract

Background - We hypothesized that collagenolytic activity produced by activated macrophages contributes to collagen loss and the subsequent instability of atheromatous lesions, a common trigger of acute coronary syndromes. However, no direct in vivo evidence links collagenases with the regulation of collagen content in atherosclerotic plaques. Methods and Results - To test the hypothesis that collagenases influence the structure of atheromata, we examined collagen accumulation in atherosclerotic lesions of apolipoprotein E-deficient mice (apoE-/-) that express collagenase-resistant collagen-I (ColR/R/apoE-/-, n=12) or wild-type collagen-expressing mice (Col+/+/apoE-/-, n = 12). Aortic atheromata of both groups had similar sizes and numbers of macrophages, a major source of collagenases. However, aortic intimas from ColR/R/apoE -/- mice contained fewer smooth muscle cells, a source of collagen, probably because of decreased migration or proliferation or increased cell death. Despite reduced numbers of smooth muscle cells, atheromata of Col R/R/apoE-/- mice contained significantly more intimal collagen than did those of Col+/+/apoE-/- mice. Conclusion - These results establish that collagenase action regulates plaque collagen turnover and smooth muscle cell accumulation.

Original languageEnglish
Pages (from-to)1953-1959
Number of pages7
JournalCirculation
Volume110
Issue number14
DOIs
Publication statusPublished - 2004 Oct 5
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Fukumoto, Y., Deguchi, J. O., Libby, P., Rabkin-Aikawa, E., Sakata, Y., Chin, M. T., Hill, C. C., Lawler, P. R., Varo, N., Schoen, F. J., Krane, S. M., & Aikawa, M. (2004). Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques. Circulation, 110(14), 1953-1959. https://doi.org/10.1161/01.CIR.0000143174.41810.10