Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice

Increased plasma concentrations of angiotension II (Ang II) have been impli cated in atherogenesis. To examine this relationship directly, we infused A ng II or vehicle for 1 month via osmotic minipumps into mature apoE(-/-) mi ce. These doses of Ang LI did not alter arterial blood pressure, body weigh t, serum cholesterol concentrations, or distribution of lipoprotein cholest erol. However, Ang II infusions promoted an increased severity of aortic at herosclerotic lesions. These Ang II-induced lesions were predominantly lipi d-laden macrophages and lymphocytes; moreover, Ang II promoted a marked inc rease in the number of macrophages present in the adventitial tissue underl ying lesions. Unexpectedly, pronounced abdominal aortic aneurysms were pres ent in apoE(-/-) mice infused with Ang II. Sequential sectioning of aneurys mal abdominal aorta revealed two major characteristics: an intact artery th at is surrounded by a large remodeled adventitia, and a medial break with p ronounced dilation and more modestly remodeled adventitial tissue. Although no atherosclerotic lesions were visible at the medial break point, the pre sence of hyperlipidemia was required because infusions of Ang II into apoE( +/+) mice failed to generate aneurysms. These results demonstrate that incr eased plasma concentrations of Ang II have profound and rapid effects on va scular pathology when combined with hyperlipidemia, in the absence of hemod ynamic influences.