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


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.
Shi
Weibin
W
Department of Radiology, University of Virginia, Charlottesville 22908, USA. ws4v@virginia.edu
Brown
Morry D
MD
Wang
Xuping
X
Wong
Jack
J
Kallmes
David F
DF
Matsumoto
Alan H
AH
Helm
Gregory A
GA
Drake
Thomas A
TA
Lusis
Aldons J
AJ
D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D004032:Diet; D005260:Female; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010641:Phenotype; D017540:Tunica Media / Q000473:pathology
D001057:Apolipoproteins E; D008055:Lipids; D020782:Matrix Metalloproteinases