Endogenously increased angiotensin II in hypertensive ApoE-/- mice induced vulnerable plaques with thinner fibrous caps, larger lipid cores, and increased macrophage content (all P<0.01).
p-value: p=<0.01
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. Splenocytes from high angiotensin II ApoE-/- mice produced significantly higher amounts of interferon (IFN)-gamma than those from ApoE-/- mice with normal angiotensin II; secretion of IL4 and IL10 was not different. In addition, we provide evidence for a direct stimulating effect of angiotensin II on lymphocyte IFN-gamma production. These findings suggest a new mechanism in plaque vulnerability demonstrating that angiotensin II, within the context of hypertension and hypercholesterolemia, independently from its hemodynamic effect behaves as a local modulator promoting the induction of vulnerable plaques probably via a T helper switch.
Mazzolai et al. (Tue,) conducted a other in Atherosclerotic plaque vulnerability. Endogenously increased angiotensin II production vs. Normal angiotensin II production was evaluated on Plaque vulnerability (fibrous cap thickness, lipid core size, macrophage content) (p=<0.01). Endogenously increased angiotensin II in hypertensive ApoE-/- mice induced vulnerable plaques with thinner fibrous caps, larger lipid cores, and increased macrophage content (all P<0.01).