title: Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with Marfan syndrome.
abstract: BACKGROUND
  Marfan syndrome (MFS) is known to cause ascending thoracic aortic aneurysms (ATAAs). Transforming growth factor beta (TGF-beta) has recently been implicated in this process. Imbalances between the matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) have also been shown to contribute to aneurysm formation. Whether and to what degree MMP, TIMP, and TGF-beta signaling profiles are altered in ATAAs in MFS compared with non-MFS patients remains unknown.
  
  
  RESULTS
  ATAA samples taken during aortic replacement from age-matched MFS (n=9) and non-MFS (n=18) patients were assessed for representative subtypes of all MMP classes, all 4 known TIMPs, and type 2 TGF-beta receptors (TGFBR2). Results were expressed as a percentage (mean+/-SEM) of reference control samples (100%; n=18) obtained from patients without ATAA. In MFS, decreased MMP-2 (76+/-7; P<0.05 versus control), increased MMP-12 (161+/-27% versus control; P<0.05), and increased MT1-MMP (248+/-64% versus 91+/-21 non-MFS and control; P<0.05) were observed. TIMP-3 (74+/-23%) was reduced compared with control values (P<0.05) and TIMP-2 was elevated (128+/-31%) compared with non-MFS (73+/-19%; P<0.05). In non-MFS samples, MMP-1 (70+/-16%), MMP-3 (77+/-18%), MMP-8 (75+/-11%), MMP-9 (69+/-14%), and MMP-12 (85+/-15%) were decreased compared with control (P<0.05). TIMPs 1 to 3 were reduced in non-MFS compared with control values (P<0.05). TGFBR2 were increased in MFS (193+/-32%) compared with non-MFS (95+/-16%) and controls (P<0.05).
  
  
  CONCLUSIONS
  A unique MMP and TIMP portfolio was observed in ATAAs from MFS compared with non-MFS patients. In addition, MFS samples showed evidence of increased TGF-beta signaling. These differences suggest disparate mechanisms of extracellular matrix remodeling between these 2 groups of patients.
authors.affiliation: Cardiothoracic Surgical Research, Division of Cardiothoracic Surgery, Medical University of South Carolina, Ralph H. Johnson Veterans Affairs Medical Center, Suite 409 CSB, 96 Jonathan Lucas St, Charleston, SC 29425, USA. ikonomij@musc.edu
authors.forename: John S
authors.initials: JS
authors.lastname: Ikonomidis
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Jones
authors.forename: John R
authors.initials: JR
authors.lastname: Barbour
authors.forename: Robert E
authors.initials: RE
authors.lastname: Stroud
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Clark
authors.forename: Brooke S
authors.initials: BS
authors.lastname: Kaplan
authors.forename: Ahmed
authors.initials: A
authors.lastname: Zeeshan
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Bavaria
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
mesh_terms: D000328:Adult; D000784:Aortic Dissection / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D001011:Aorta / Q000378:metabolism*; D017545:Aortic Aneurysm, Thoracic / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D019917:Blood Vessel Prosthesis Implantation; D004198:Disease Susceptibility; D005260:Female; D000071837:Fibrillins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000150:complications*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008840:Microfilament Proteins / Q000172:deficiency / Q000378:metabolism; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D000071837:Fibrillins; D008840:Microfilament Proteins; D018125:Receptors, Transforming Growth Factor beta; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated