title: Effects of deletion of the matrix metalloproteinase 9 gene on development of murine thoracic aortic aneurysms.
abstract: BACKGROUND
  The matrix metalloproteinases (MMPs) contribute to cardiovascular remodeling, and MMPs, such as the gelatinases (MMP-9 and MMP-2), have been identified in thoracic aortic aneurysmal (TAA) tissue, but a cause-effect relationship has not been clearly established. Accordingly, this study examined TAA progression in mice devoid of the MMP-9 gene.
  
  
  RESULTS
  The descending thoracic aortas of wild-type (WT) FVB (n =17) and MMP-9 gene knockout (KO, n =11) mice were exposed to 0.5 mol/L of CaCl2 for 15 minutes with terminal studies performed at 4 weeks. Aortic lumen diameter was measured using video micrometry at baseline and at 4 weeks (TAA) followed by aortic tissue analysis. In WT mice, aortic diameter increased by 138+/-5% at 4 weeks (P<0.05), consistent with TAA formation. In the KO mice, aortic diameter increased from baseline by 120+/-4% (P<0.05) but was attenuated from WT TAA values (P<0.05). Gelatin zymography performed on TAA segments confirmed the absence of MMP-9 in the KO mice but a >8-fold relative increase in the active form of MMP-2 compared with WT (P<0.05). Despite this, MMP-2 activity was relatively increased (P<0.05) and colocalized to smooth muscle cell actin in a differential pattern favoring medial distruction in the WT TAA compared with the KO TAA segments.
  
  
  CONCLUSIONS
  These results demonstrate that MMP-9 gene deletion attenuated TAA formation despite an increase in the zymographic levels of MMP-2. These unique findings suggest that an interaction between these 2 MMPs is necessary to facilitate TAA progression.
authors.affiliation: Division of Cardiothoracic Surgery, Medical University of South Carolina, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA. ikonomij@musc.edu
authors.forename: John S
authors.initials: JS
authors.lastname: Ikonomidis
authors.forename: John R
authors.initials: JR
authors.lastname: Barbour
authors.forename: Zainab
authors.initials: Z
authors.lastname: Amani
authors.forename: Robert E
authors.initials: RE
authors.lastname: Stroud
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Herron
authors.forename: David M
authors.initials: DM
authors.lastname: McClister
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Camens
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
authors.forename: Rupak
authors.initials: R
authors.lastname: Mukherjee
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D002122:Calcium Chloride / Q000633:toxicity; D018450:Disease Progression; D004790:Enzyme Induction; D053508:Matrix Metalloproteinase 12; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008666:Metalloendopeptidases / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout
chemical_list: D000199:Actins; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12; D002122:Calcium Chloride