Angiotensin II Induces Region-Specific Medial Disruption during Evolution of Ascending Aortic Aneurysms

Abstract

Angiotensin II (AngII) promotes development of ascending aortic aneurysms (AAs), but progression of this pathology is undefined. We evaluated factors potentially involved in progression, and determined the temporal sequence of tissue changes during development of AngII-induced ascending AAs. AngII infusion into C57BL/6J mice promoted rapid expansion of the ascending aorta, with significant increases within 5 days, as determined by both invivo ultrasonography and exvivo sequential acquisition of tissues. Rates of expansion were not significantly different in LDL receptor-null mice fed a saturated fat-enriched diet, demonstrating a lack of effect of hypercholesterolemia. Augmenting systolic blood pressure with norepinephrine infusion had no significant effect on ascending aortic expansion. Pathological changes observed within 5 days of AngII infusion included increased medial thickness and intramural hemorrhage characterized by erythrocyte extravasation in outer lamellar layers of the media. Intramedial hemorrhage was not observed after prolonged AngII infusion, although partial medial disruption was present. Elastin fragmentation and transmural medial breaks of the ascending aorta were observed with continued AngII infusion, which were restricted to anterior aspects. CD45(+) cells accumulated in adventitia but were minimal in media. Similar pathology was observed in tissues obtained from patients with ascending AAs. In conclusion, AngII promotes ascending AAs through region-specific changes that are independent of hypercholesterolemia or systolic blood pressure.