title: Ascending Aortic Aneurysm in Angiotensin II-Infused Mice: Formation, Progression, and the Role of Focal Dissections.
abstract: OBJECTIVE
  To understand the anatomy and physiology of ascending aortic aneurysms in angiotensin II-infused ApoE(-/-) mice.
  
  
  RESULTS
  We combined an extensive in vivo imaging protocol (high-frequency ultrasound and contrast-enhanced microcomputed tomography at baseline and after 3, 10, 18, and 28 days of angiotensin II infusion) with synchrotron-based ultrahigh resolution ex vivo imaging (phase contrast X-ray tomographic microscopy) in n=47 angiotensin II-infused mice and 6 controls. Aortic regurgitation increased significantly over time, as did the luminal volume of the ascending aorta. In the samples that were scanned ex vivo, we observed one or several focal dissections, with the largest located in the outer convex aspect of the ascending aorta. The volume of the dissections moderately correlated to the volume of the aneurysm as measured in vivo (r(2)=0.46). After 3 days of angiotensin II infusion, we found an interlaminar hematoma in 7/12 animals, which could be linked to an intimal tear. There was also a significant increase in single laminar ruptures, which may have facilitated a progressive enlargement of the focal dissections over time. At later time points, the hematoma was resorbed and the medial and adventitial thickness increased. Fatal transmural dissection occurred in 8/47 mice at an early stage of the disease, before adventita remodeling.
  
  
  CONCLUSIONS
  We visualized and quantified the dissections that lead to ascending aortic aneurysms in angiotensin II-infused mice and provided unique insight into the temporal evolution of these lesions.
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.). bram.trachet@epfl.ch.
authors.forename: Bram
authors.initials: B
authors.lastname: Trachet
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Piersigilli
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.).
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Fraga-Silva
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.).
authors.forename: Lydia
authors.initials: L
authors.lastname: Aslanidou
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.).
authors.forename: Jessica
authors.initials: J
authors.lastname: Sordet-Dessimoz
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Astolfo
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.).
authors.forename: Marco F M
authors.initials: MF
authors.lastname: Stampanoni
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Segers
authors.affiliation: From the Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (B.T., R.A.F.-S., L.A., N.S.); IBiTech-bioMMeda, Ghent University-iMinds Medical IT, Ghent, Belgium (B.T., P.S.); School of Life Sciences, PTEC GE, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (A.P.); Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland (A.P.); Histology Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland (J.S.-D.); Swiss Light Source, Paul Scherrer Institut, Villigen, Switzerland (A.A., M.F.M.S.); and Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland (M.F.M.S.).
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Stergiopulos
mesh_terms: D000784:Aortic Dissection / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology*; D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology*; D001019:Aortic Rupture / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology*; D001022:Aortic Valve Insufficiency / Q000209:etiology; D001027:Aortography / Q000379:methods; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D018450:Disease Progression; D004547:Elastic Tissue / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors; D018617:Ultrasonography, Doppler, Pulsed; D066253:Vascular Remodeling; D055114:X-Ray Microtomography
chemical_list: D001057:Apolipoproteins E; D000804:Angiotensin II
keywords: aortic aneurysm; aortic dissection; ascending aorta; cardiovascular imaging; mouse models of human disease