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 Citations (Scopus)

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 2003
Externally publishedYes

Fingerprint

Apolipoproteins E
Matrix Metalloproteinase 9
Matrix Metalloproteinase 12
Matrix Metalloproteinase 2
Macrophages
Aorta
Genetic Background
Aortic Aneurysm
Gelatin
Caseins
Matrix Metalloproteinases
Dilatation
Atherosclerosis

Keywords

  • Aortic aneurysms
  • Atherosclerosis
  • Genetic predisposition
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Genetic backgrounds but not sizes of atherosclerotic lesions determine medial destruction in the aortic root of apolipoprotein E-deficient mice. / Shi, Weibin; Brown, Morry D.; Wang, Xuping; Wong, Jack; Kallmes, David F; Matsumoto, Alan H.; Helm, Gregory A.; Drake, Thomas A.; Lusis, Aldons J.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 10, 10.2003, p. 1901-1906.

Research output: Contribution to journalArticle

Shi, Weibin ; Brown, Morry D. ; Wang, Xuping ; Wong, Jack ; Kallmes, David F ; Matsumoto, Alan H. ; Helm, Gregory A. ; Drake, Thomas A. ; Lusis, Aldons J. / Genetic backgrounds but not sizes of atherosclerotic lesions determine medial destruction in the aortic root of apolipoprotein E-deficient mice. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 ; Vol. 23, No. 10. pp. 1901-1906.
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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.",
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AU - Shi, Weibin

AU - Brown, Morry D.

AU - Wang, Xuping

AU - Wong, Jack

AU - Kallmes, David F

AU - Matsumoto, Alan H.

AU - Helm, Gregory A.

AU - Drake, Thomas A.

AU - Lusis, Aldons J.

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N2 - 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.

AB - 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.

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