Increased plasma concentrations of angiotension II (Ang II) have been implicated in
atherogenesis. To examine this relationship directly, we infused Ang II or vehicle for 1 month via osmotic minipumps into mature
apoE(-/-) mice. These doses of Ang II did not alter arterial blood pressure,
body weight, serum
cholesterol concentrations, or distribution of
lipoprotein cholesterol. However, Ang II infusions promoted an increased severity of aortic atherosclerotic lesions. These Ang II-induced lesions were predominantly
lipid-laden macrophages and lymphocytes; moreover, Ang II promoted a marked increase in the number of macrophages present in the adventitial tissue underlying lesions. Unexpectedly, pronounced
abdominal aortic aneurysms were present in
apoE(-/-) mice infused with Ang II. Sequential sectioning of aneurysmal abdominal aorta revealed two major characteristics: an intact artery that is surrounded by a large remodeled adventitia, and a medial break with pronounced dilation and more modestly remodeled adventitial tissue. Although no atherosclerotic lesions were visible at the medial break point, the presence of
hyperlipidemia was required because infusions of Ang II into
apoE(+/+) mice failed to generate
aneurysms. These results demonstrate that increased plasma concentrations of Ang II have profound and rapid effects on vascular pathology when combined with
hyperlipidemia, in the absence of hemodynamic influences.