title: Angiotensin II induces region-specific medial disruption during evolution of ascending aortic aneurysms.
abstract: Angiotensin II (Ang II) 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 Ang II-induced ascending AAs. Ang II infusion into C57BL/6J mice promoted rapid expansion of the ascending aorta, with significant increases within 5 days, as determined by both in vivo ultrasonography and ex vivo 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 Ang II 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 Ang II infusion, although partial medial disruption was present. Elastin fragmentation and transmural medial breaks of the ascending aorta were observed with continued Ang II 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, Ang II promotes ascending AAs through region-specific changes that are independent of hypercholesterolemia or systolic blood pressure.
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Rateri
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Davis
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Anju
authors.initials: A
authors.lastname: Balakrishnan
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Howatt
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Moorleghen
authors.affiliation: Department of Pathology, University of Kentucky, Lexington, Kentucky.
authors.forename: William N
authors.initials: WN
authors.lastname: O'Connor
authors.affiliation: Department of Biostatistics, University of Kentucky, Lexington, Kentucky.
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky. Electronic address: alan.daugherty@uky.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000473:pathology*; D001014:Aortic Aneurysm / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017540:Tunica Media / Q000473:pathology*
chemical_list: D000804:Angiotensin II