Boston - American Association for Thoracic Surgery

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89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTSF6. Smooth Muscle Phenotypic Modulation Is an Early Event inMurine Aortic Aneurysms and Human AneurysmsGorav Ailawadi, † Sandra P. Walton, Hong Pei, Chris W. Moehle, ZequanYang, Christine Lau, ∞ Mark C. Mochel, Irving L. Kron, * Gary K. OwensTCV Surgery, University of Virginia, Charlottesville, VA, USAInvited Discussant: John S. IkonomidisOBJECTIVE: Vascular smooth muscle cells (SMCs) have the ability to undergoprofound changes in phenotype, defined by coordinated repression of SMC markergenes and production of matrix metalloproteinases (MMPs), in models of atherosclerosis.In aneurysm development, studies have primarily focused on the role ofleukocytes, while little is known of the role of SMCs. We hypothesized that SMCsundergo phenotypic modulation in experimental and human aortic aneurysms(AAs) and that his event is an early event in disease progression.METHODS: Abdominal aortas from wild type C57B6 mice (n = 56) were perfusedwith elastase or saline (control) and harvested at 1, 3, 7 or 14 days. Aorticdiameter was measured using video micrometry pre-perfusion and at harvest.Aortas were analyzed by real time-PCR and immunohistochemistry for a numberof smooth muscle marker genes, including SM22α, SMα-actin, SM MHC, as well asMMP-2,-9. In complimentary experiments, human ascending aneurysmal aortas(n = 10) undergoing open repair and control aorta from patients undergoing coronaryartery bypass grafting (n = 10) were harvested and analyzed by immunohistochemistry.RESULTS: Aortic diameter in elastase perfused mice was similar to saline perfusedmice at 7 days (60.0 ± 9.13% versus 53.3 ± 18.3%, P = .49). At 14 days, aorticdiameter was significantly larger following elastase perfusion (100 ± 9.6% versus59.5 ± 18.9%, P = .0002). By 7 days, elastase perfused mice had significant downregulationof SM22α (0.72 ± 2.62 versus 12.19 ± 2.35, P < .0001) and SMα-actin (0.27± 2.84 versus 10.97 ± 1.97, P < .0001) expression compared to saline perfused animalswell before the aneurysm phenotype was present. At 14 days, SM22α (1.43 ±0.88 versus 3.26 ± 1.54, P = .05) and SMα-actin (3.73 ± 0.20 vs. 6.51 ± 1.74, P = .02)expression remained less in aneurysmal aortas. Immunohistochemistry confirmedmarkedly less SM22α and SMα-actin in experimental aneurysms in concert withincreased MMP2,-9 staining at 7 and 14 days. Similarly, human aneurysms had lessSM22α and SMα-actin and increased MMP-9 staining by immunohistochemistrycompared to control aorta.CONCLUSION: Experimental murine and human aneurysms demonstratesmooth muscle cell phenotypic modulation characterized by downregulation ofsmooth muscle marker genes and upregulation of MMPs. These events in experimentalmodels occur early prior to aneurysm formation. Targeting SMCs to a reparativephenotype may provide a novel therapy in the treatment of aortic aneurysms.* AATS Member† Resident Traveling Fellowship 2006∞ John W. Kirklin Research Scholarship 2006130
AMERICAN ASSOCIATION FOR THORACIC SURGERYF7. Biodegradable Synthetic Small-Calibre Vascular Grafts:Long-Term Results After Replacement of the Rat AortaBeat H. Walpoth, 1 Damiano Mugnai, 1 Jean-Christophe Tille, 2Francesco Innocente, 1 Benjamin Nottelet, 3 Corinne Berthonneche, 4Xavier Montet, 5 Sarra de Valence, 3 Michael Moeller, 3 Robert Gurny, 3Afksendiyos Kalangos 11. Department of Cardiovascular Surgery, University Hospital of Geneva, Geneva,Switzerland; 2. Department of Pathology, University Hospital of Geneva,Geneva, Switzerland; 3. Department of Pharmaceutics & BiopharmaceuticsEPGL, University of Geneva, Geneva, Switzerland; 4. Department of Medicine,University Hospital of Lausanne, Lausanne, Switzerland; 5. Department ofRadiology, University Hospital of Geneva, Geneva, SwitzerlandInvited Discussant: Gorav AilawadiOBJECTIVE: Shelf-ready synthetic small calibre grafts are needed for coronaryartery bypass grafting. Biodegradable scaffolds resistant to degradation-inducedaneurysm formation in the systemic arterial circulation have been developed for invivo vascular tissue engineering. Our aim is to assess the long-term results of synthetic,biodegradable small-calibre vascular grafts compared to ePTFE for aorticreplacement in the rat model.TUESDAYMorningMETHODS: Ten anaesthetised Sprague Dawley rats (male, 275g), received aninfrarenal aortic graft (5 biodegradable; 5 ePTFE) replacement (end-to-end; 2 mmID; 20 mm long) and 5 rats served as shame controls. Biodegradable grafts (polycaprolactone= PCL) were produced by random nano-fibre (porosity 80%) electrospinning.After 1-year survival in vivo high resolution ultra-sonography (Visualsonics;see figure) and angiography were performed to assess patency, stenosis,aneurysm formation, intimal hyperplasia and compliance. After explantationmicro CT calcification quantification, histology, immuno-histology, scanning electronmicroscopy (SEM) and morphometry were carried out.RESULTS: All grafts (PCL and ePTFE) showed 100% patency at 12 months. Noaneurysmal dilation or stenoses were found in the PCL group by angiography.Ultra-sonography showed minimal peri-anastomotic intimal hyperplasia in PCL131
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AATS FUTURE MEETINGSMay 1-5, 2010Me
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