title: Matrix metalloproteinase 14 and 19 expression is associated with thoracic aortic aneurysms.
abstract: OBJECTIVE
  It is hypothesized that an altered turnover of extracellular matrix mediated by matrix metalloproteinases (MMPs) is present in thoracic aortic aneurysms. Here, we analyzed the occurrence of MMPs and MMP inhibitors in ascending aortic aneurysms in patients with bicuspid and tricuspid aortic valves.
  
  
  METHODS
  Expression of 23 MMPs and their inhibitors was measured in aortic intima/media and adventitia in 109 patients (40 tricuspid, 69 bicuspid, 68 with aortic diameter≥4.5 cm, and 41 with ≤4.0 cm) using Affymetrix Exon arrays (Affymetrix, Santa Clara, Calif). Gene expression was confirmed by quantitative real-time polymerase chain reaction. Principal components analysis was used to study differences in gene expression. Immunohistochemistry was used to study protein expression.
  
  
  RESULTS
  We detected messenger RNA expression for gelatinases (MMP2 and MMP9), stromelysin 3 (MMP11), all membrane bound MMPs (MMP14, MMP15, MMP16, MMP17, MMP24, MMP25), MMP19, MMP21, and MMP28 in ascending aorta. No expression of collagenases was detected. Principal components analysis showed that changes in mRNA expression between dilated and nondilated aorta were mainly detected in patients with tricuspid aortic valves. MMP14 and MMP19 showed higher expression in dilated aortas and MMP19 expression correlated positively to maximal aortic diameter in patients with tricuspid aortic valves (Rho=0.61, P=.004, and Rho=0.57, P=.008, using raw and body surface area-corrected aortic diameter, respectively). Immunohistochemical staining demonstrated increased medial expression of MMP14 and MMP19 in dilated aorta.
  
  
  CONCLUSIONS
  The present study identifies MMP14 and MMP19 as proteolytic enzymes potentially involved in aneurysm formation in the ascending aorta of patients with tricuspid aortic valves.
authors.affiliation: Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. veronica.jackson@karolinska.se
authors.forename: Veronica
authors.initials: V
authors.lastname: Jackson
authors.forename: Therese
authors.initials: T
authors.lastname: Olsson
authors.forename: Sanela
authors.initials: S
authors.lastname: Kurtovic
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.forename: Valentina
authors.initials: V
authors.lastname: Paloschi
authors.forename: Dick
authors.initials: D
authors.lastname: Wågsäter
authors.forename: Anders
authors.initials: A
authors.lastname: Franco-Cereceda
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; C108362:matrix metalloproteinase 19; D053511:Matrix Metalloproteinase 14