Details

Autor(en) / Beteiligte

• Mazzolai, Lucia
• Duchosal, Michel A
• Korber, Martine
• Bouzourene, Karima
• Aubert, Jean François
• Hao, Hiroyuki
• Vallet, Veronique
• Brunner, Hans-R
• Nussberger, Jürg
• Gabbiani, Giulio
• Hayoz, Daniel

Titel

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

Ist Teil von

• Hypertension (Dallas, Tex. 1979), 2004-09, Vol.44 (3), p.277-282

Ort / Verlag

Philadelphia, PA: American Heart Association, Inc

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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)-γ 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-γ 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.