Endogenous Angiotensin II Induces Atherosclerotic Plaque Vulnerability and Elicits a Th1 Response in ApoE −/− Mice

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Abstract
Rupture of vulnerable plaques is the main cause of acute cardiovascular events. However, mechanisms responsible for transforming a stable into a vulnerable plaque remain elusive. Angiotensin II, a key regulator of blood pressure homeostasis, has a potential role in atherosclerosis. To study the contribution of angiotensin II in plaque vulnerability, we generated hypertensive hypercholesterolemic ApoE−/− mice with either normal or endogenously increased angiotensin II production (renovascular hypertension models). Hypertensive high angiotensin II ApoE−/− mice developed unstable plaques, whereas in hypertensive normal angiotensin II ApoE−/− mice plaques showed a stable phenotype. Vulnerable plaques from high angiotensin II ApoE−/− mice had thinner fibrous cap (P<0.01), larger lipid core (P<0.01), and increased macrophage content (P<0.01) than even more hypertensive but normal angiotensin II ApoE−/− mice. Moreover, in mice with high angiotensin II, a skewed T helper type 1-like phenotype was observed. Spleno...