Advanced atherosclerotic lesions in the innominate artery of the ApoE knockout mouse

Most previous studies of atherosclerosis in hyperlipidemic mouse models hav e focused their investigations on lesions within the aorta or aortic sinus in young animals. None of these studies has demonstrated clinically signifi cant advanced lesions. We previously mapped the distribution of lesions thr oughout the arterial tree of apolipoprotein E knockout (apoE(-/-)) mice bet ween the ages of 24 and 60 weeks. We found that the innominate artery, a sm all vessel connecting the aortic arch to the right subclavian and right car otid artery, exhibits a highly consistent rate of lesion progression and de velops a narrowed vessel characterized by atrophic media and perivascular i nflammation. The present study reports the characteristics of advanced lesi ons in the innominate artery of apoE(-/-) mice aged 42 to 60 weeks. In anim als aged 42 to 54 weeks, there is a very high frequency of intraplaque hemo rrhage and a fibrotic conversion of necrotic zones accompanied by loss of t he fibrous cap. By 60 weeks of age, the lesions are characterized by the pr esence of collagen-rich fibrofatty nodules often flanked by lateral xanthom as. The processes underlying these changes in the innominate artery of olde r apoE(-/-) mice could well be a model for the critical processes leading t o the breakdown and healing of the human atherosclerotic plaque.