title: Background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility.
abstract: OBJECTIVE
  Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression.
  
  
  METHODS
  Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured.
  
  
  RESULTS
  Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0% ± 13.6 increase compared to 57.8% ± 6.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5 kPa ± 93.6 versus 621.4 kPa ± 84.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size.
  
  
  CONCLUSIONS
  These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. Intrinsic properties of the aorta between the two strains of mice, including baseline expression of MMP-2, influence susceptibility to AAA.
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Dale
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Suh
authors.affiliation: Department of Mechanical & Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Shijia
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Meisinger
authors.affiliation: Department of Mechanical & Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Linxia
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
authors.forename: Vicki J
authors.initials: VJ
authors.lastname: Swier
authors.affiliation: Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Carson
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: B Timothy
authors.initials: BT
authors.lastname: Baxter
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: wxiong@unmc.edu.
authors.forename: Wanfen
authors.initials: W
authors.lastname: Xiong
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation; D002122:Calcium Chloride; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D055119:Elastic Modulus; D020022:Genetic Predisposition to Disease; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000378:metabolism; D013045:Species Specificity; D014333:Tropoelastin / Q000378:metabolism; D015854:Up-Regulation; D059289:Vascular Stiffness
chemical_list: D014333:Tropoelastin; D010196:Pancreatic Elastase; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002122:Calcium Chloride
keywords: Aneurysm; Aorta; Matrix metalloproteinase