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.

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.