Angiotensin II induces region-specific medial disruption during evolution of ascending aortic aneurysms

Debra L. Rateri, Frank M. Davis, Anju Balakrishnan, Deborah A. Howatt, Jessica J. Moorleghen, William N. O'Connor, Richard Charnigo, Lisa A. Cassis, Alan Daugherty

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

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.

Original languageEnglish
Pages (from-to)2586-2595
Number of pages10
JournalAmerican Journal of Pathology
Volume184
Issue number9
DOIs
StatePublished - Sep 2014

Bibliographical note

Funding Information:
Supported by NIH grants R01-HL107319 (A.D.) and P20-GM103527 (L.A.C.) and a Sarnoff Cardiovascular Foundation Fellowship (F.M.D.).

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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