198S
Journal of Vascular Surgery
Abstracts
June Supplement 2017 within tobacco smoke have not been differentiated. The objective of this study was to compare the cellular effects of tobacco smoke vs nicotine on human aortic smooth muscle cells (HASMCs) and to look at the histologic changes in the aorta of wild-type (WT) and hyperlipidemic (apolipoprotein E knockout) mice exposed to solubilized tobacco smoke. Methods: We treated HASMCs with differing dilutions of solubilized tobacco smoke (2 cigarettes solubilized per 1 mL of buffer) to look at the relationship between solubilized tobacco smoke or nicotine concentration and cell death. Osmotic pumps with solubilized tobacco smoke were implanted into both WT and hyperlipidemic mice to investigate the effects of solubilized tobacco smoke exposure on the mouse aorta. Histologic and cellular changes in the abdominal
and thoracic aorta where assessed with standard immunohistochemical methods. Results: Treatment of HASMCs with solubilized tobacco smoke at dilutions higher than 1:1000 induce cell death while treatment of HASMCs with a nicotine-only solution with similar nicotine concentration (1.25 mg/mL) as the solubilized tobacco smoke did not. Treatment of WT mice with solubilized tobacco smoke resulted in elastin breaks in the aorta without a cellular infiltrate (Fig 1). Treatment of hyperlipidemic mice with solubilized tobacco smoke resulted in development of plaques in 67% of mice vs 0% of controls (Fig 2). A total of 33% of the mice developed plaques in the abdominal aorta while 50% developed plaques in the thoracic aorta (17% had plaques in both). Conclusions: This study describes the early aortic changes caused by tobacco smoke exposure and differentiates between the effects of tobacco smoke vs nicotine alone. Solubilized tobacco smoke induces aortic smooth muscle cell death in vitro, while nicotine does not. In vivo, solubilized tobacco smoke causes breakage of elastin fibers without inciting and inflammatory infiltrate and can enhance atherosclerotic plaque formation in hyperlipidemic mice. Author Disclosures: C. Abraham: Nothing to disclose; A. Azarbal: Nothing to disclose; G. Landry: Nothing to disclose; E. Manalo: Nothing to disclose; G. Moneta: Nothing to disclose; T. L. Repella: Nothing to disclose; L. Y. Sakai: Nothing to disclose.
PC220. Angiotensin 1-7 Suppresses Experimental Abdominal Aortic Aneurysms
Fig 1. Treatment of wild-type mice with solubilized tobacco smoke results in elastin breaks in the aorta without a cellular infiltrate. These are representative images of (A) abdominal aorta of mice treated with phosphate-buffed saline, (B and C) abdominal aorta of mice treated with solubilized smoke solution via a subcutaneous osmotic pump, and (D) abdominal aorta of mice treated with solubilized smoke solution via a peritoneal osmotic pump. The arrows indicate areas of elastin breaks.
Fig 2. Treatment of hyperlipidemic mice with solubilized tobacco smoke results in plaque formation. These are representative images of (A) abdominal aorta of hyperlipidemic mice treated with phosphatebuffed saline, (B) thoracic aorta, or (C) abdominal aorta of hyperlipidemic mice treated with solubilized smoke solution via a subcutaneous osmotic pump, and (D) abdominal aorta of hyperlipidemic mice treated with solubilized smoke solution via a peritoneal osmotic pump.
Gang Li,1 Baohui Xu,1 Hongping Deng,1 Anna Cabot,1 Hai Yuan,2 Xuejun Wu,2 Sara A. Michie,1 Ronald L. Dalman1. 1Stanford University School of Medicine, Stanford, Calif; 2Shandong University School of Medicine, China (People’s Republic) Objectives: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease, the pathogenesis of which remains incompletely defined. We and other investigators have demonstrated the critical importance of angiotensin (Ang) II and its cellular receptor AT1 in the development of experimental AAAs. Although Ang 1-7 and its receptor Mas counteract many cellular functions mediated by AT1, the role of the Ang 1-7/Mas pathway has not been investigated in this context. This study evaluated the influences of Ang 1-7 and its receptor Mas on the formation and progression of experimental AAAs. Methods: AAAs were created in 10- to 12-week-old male C57BL/6J mice via intra-aortic infusion of porcine pancreatic elastase (PPE). Mice were treated with Ang 1-7 (0.5 mg/kg/d via subcutaneous injection) beginning immediately before or 4 days after PPE infusion. Another cohort of mice were cotreated with Ang 1-7 and the Mas receptor antagonist A779 (0.5 mg/kg/day) beginning immediately before PPE infusion. Control mice were treated with equal amounts of vehicle (phosphate-buffered saline) in identical regimens. Influences on AAA formation and progression were evaluated by serial assessment of aortic diameter in vivo and aortic histology at sacrifice. Results: The Fig summarizes major influences of the Ang 1-7/Mas receptor pathway on aneurysm formation, progression, and histopathology. In ultrasound imaging at 14 days, Ang 1-7 treatment initiated immediately following aneurysm creation substantially suppressed aortic enlargement compared to vehicle treatment. Histologically, Ang 1-7 treatment was associated with attenuation of aortic medial elastin and smooth muscle cell depletion, mural macrophage, CD4 + , CD8 + T- and B-cell density and neoangiogenesis. Cotreatment with the Ang 1-7 receptor Mas antagonist A779 “rescued” the aneurysm phenotype. Additionally, Ang 1-7 treatment initiated even 4 days following AAA creation was still effective in limiting further aneurysmal enlargement and pathologic evolution. Conclusions: Ang 1-7 treatment, initiated either at or up to 4 days following AAA initiation limits further progression of experimental AAAs. This inhibitory effect seems likely related to activation of the Mas receptor. These results suggest that either Ang 1-7 or alternative Mas receptor agonists may have clinical utility in suppressing progression of early AAA disease.
Journal of Vascular Surgery
Abstracts
199S
Volume 65, Number 6S accurate than the 2.5-mm probe. The organization of the graft fibers around the hole was not distorted by the laser or by successive dilatations. The optimal sequence to create a Lf was defined as hole creation using a 0.9-mm laser probe, predilatation with a 2-mm standard angioplasty balloon, followed by a 2.5 mm cutting balloon, then a 4-mm balloon, and deployment of a 5- or 6-mm covered stent that was subsequently flared. Examination of the Lf confirmed a prosthetic continent coverage of the origin of the covered stent (Fig 1). The Lf remained stable despite major angulation of the covered stent (Fig 2). Conclusions: Expanded polytetrafluoroethylene covered endografts are not suitable for laser fenestration because of the difficulties to create a Lf. The optimal sequence for in situ Lf is defined and seems efficient in terms of sealing. Biomechanical studies are necessary to confirm those findings.
Fig. Angiotensin (Ang) 1-7 suppresses experimental abdominal aortic aneurysms (AAAs). Male C57BL/6J mice at age 10 to 12 weeks underwent intra-aortic porcine pancreatic elastase (PPE) infusion and received a subcutaneous injection of Ang 1-7 alone or with A779 (0.5 mg/kg/day) beginning (A-H) immediately before PPE infusion and for 14 days thereafter or beginning (I) 4 days thereafter for 10 days. A, Aortic diameter measured via ultrasound imaging. Quantification of (B) medial elastin degradation and (C) smooth muscle cell (SMC) depletion, (D) CD68þ macrophages, (E) CD4þ T cells, (F) CD8þ T cells, (G) B220þ, and (H) CD31þ neovessels. I, Influence on further aneurysm enlargement in mice with existing AAAs. All data are mean and standard deviation (n = 7-9 mice per group). ACS, Aortic cross-section. Two-way analysis of variance, followed by two-sample test, *P <.05 compared with vehicle treatment (A and I). Mann-Whitney test, .05 < #P <.1, *P <.05 and **P <.01 compared with vehicle treatment (B-H).
Author Disclosures: C. Angel: Nothing to disclose; P. Brenot: Nothing to disclose; D. Fabre: Nothing to disclose; E. Fadel: Nothing to disclose; C. Garcia Alonso: Nothing to disclose; S. Haulon: Bentley: royalties, Cook Medical and GE Healthcare: intellectual property/patents, consulting fees (eg, advisory boards); D. Verscheure: Nothing to disclose.
Author Disclosures: A. Cabot: Nothing to disclose; R. Dalman: Nothing to disclose; H. Deng: Nothing to disclose; G. Li: Nothing to disclose; S. Michie: Nothing to disclose; X. Wu: Nothing to disclose; B. Xu: Nothing to disclose; H. Yuan: Nothing to disclose.
PC222. In Vitro Analysis of Antegrade in Situ Laser Fenestration of Aortic Endografts Dorian Verscheure,1 Carlos Garcia Alonso,1 Philippe Brenot,1 Claude Angel,1 Stephan Haulon,2 Elie Fadel,1 Dominique Fabre1. 1Marie Lannelongue Hospital, Le Plessis-Robinson, France; 2University of Lille, Lille, France Objectives: In situ aortic endograft fenestrations can be performed by several methods. Retrograde laser fenestration (Lf) is used for left subclavian artery revascularization with satisfactory outcomes. We have performed antegrade fenestrations with a laser beam in the setting of complex aortic emergency repairs. The objective of this bench study was to analyze Lf performed on different aortic endografts, using microscopic and macroscopic analysis, in order to define the optimal process. Methods: Four aortic grafts were studied: Zenith (Cook Medical, Bloomington, Ind), Valiant and Endurant (Medtronic, Minneapolis, Minn), and Excluder (W. L. Gore & Associates, Flagstaff, Ariz). We created 137 Lfs using an Excimer Laser (Spectranetics, Colorado Springs, Colo), with several probe diameters. Laser probe angulation, impulsion number, and three sequences of dilatation of each Lf were evaluated. Macroscopic study was performed after deployment of a flaired covered stent. All Lf were analyzed using an optic microscope after each step until the covered stent’s deployment. Results: Laser probe angulation does not modify the Lf. Creation of a hole requires only one activation of the laser beam on the Dacron grafts, while several activations are needed with the expanded polytetrafluoroethylene covered endografts. The 0.9-mm laser probe is more
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