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.