Genetic backgrounds but not sizes of atherosclerotic lesions determine medial destruction in the aortic root of apolipoprotein E-deficient mice

Weibin Shi, Morry D. Brown, Xuping Wang, Jack Wong, David F. Kallmes, Alan H. Matsumoto, Gregory A. Helm, Thomas A. Drake, Aldons J. Lusis

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Objective - Destruction of the elastic media is the most striking histologic feature of atherosclerotic aortic aneurysms. Apolipoprotein E-deficient (apoE-/-) mice fed a Western diet develop advanced atherosclerotic lesions in the aorta. We sought to assess the integrity of atherosclerotic aortic walls in 2 apoE-/- strains, C57BL/6 (B6) and C3H/HeJ (C3H) that differ markedly in atherosclerosis susceptibility. Methods and Results - C3H.apoE-/- mice developed much smaller atherosclerotic lesions than did B6.apoE-/- mice after being fed a Western diet for 16 weeks, but the C3H.apoE-/- mice exhibited destruction of the elastic media, including erosion, fragmentation, and focal dilatation beneath plaques. Gelatin and casein zymography showed proteolytic activity of matrix metalloproteinases (MMPs) -9, -2, and -12 in aortic tissues and of MMP-9 and -12 in macrophages from both strains. However, C3H.apoE -/- mice showed significantly increased MMP-2 and -12 activity in aortas and macrophages compared with those from B6.apoE-/ - mice. MMP-9 activity was comparable in aortic tissues of the 2 strains, but it was significantly higher in macrophages from C3H.apoE -/- than from B6.apoE-/- mice. Conclusions - Data indicate that genetic backgrounds but not sizes of atherosclerotic lesions determine medial destruction in the aortic root of apoE-/- mice and that an increase in MMP proteolytic activity might contribute to the medial destruction of aortic walls in C3H.apoE-/- mice.

Original languageEnglish (US)
Pages (from-to)1901-1906
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2003

Keywords

  • Aortic aneurysms
  • Atherosclerosis
  • Genetic predisposition
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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