title: Decreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissection.
abstract: BACKGROUND
  Thoracic aortic aneurysmal diseases are characterized by degeneration of elastin within the aortic wall. Although proteinases, such as matrix metalloproteinase, appear to contribute to elastin degradation, little is known about the role of elastic fiber assembly in such diseases. Fibulin-5 is an extracellular protein that is expressed in the vascular basement membrane and regulates elastic fiber assembly by microfibril machinery. In this study, we examined whether thoracic aortic dissection (TAD) is associated with abnormal fibulin-5 expression.
  
  
  METHODS
  Intraoperative aortic samples were obtained from 21 patients with proximal aortic dissection. Control aortic tissue was obtained from 11 organ donors, heart transplant recipients, and patients undergoing coronary artery bypass. An in vitro culture of vascular smooth muscle cells was obtained from 2 TAD patients and 1 control subject. To evaluate elastin expression, we stained tissue sections with Verhoeff-Van Gieson stain. Fibulin-5 messenger RNA (mRNA) expression was determined by quantitative real-time reverse-transcriptase-polymerase chain reaction.
  
  
  RESULTS
  Aortic fibulin-5 mRNA and elastin content were decreased in TAD patients, compared with controls (P=.001 and P=.02, respectively). Decreased fibulin-5 expression strongly correlated with decreased amounts and fragmentation of elastin in aortic samples from patients with TAD (r=0.83, P < .0001 and F=20.7, P < .0001 respectively). The fibulin-5 mRNA in aortic vascular smooth muscle cells collected from TAD demonstrated a 38% decrease in expression, compared with the control.
  
  
  CONCLUSIONS
  Patients with proximal aortic dissection exhibited significantly decreased expression of aortic fibulin-5. Decreased fibulin-5 may contribute to the pathogenesis of aortic dissection by impairing elastic fiber assembly.
authors.affiliation: Section of Adult Cardiac Surgery, the Texas Heart Institute at St. Luke's Episcopal Hospital, the Division of Cardiothoracic Surgery, Baylor College of Medicine, Houston 77030, USA.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Wang
authors.forename: Scott A
authors.initials: SA
authors.lastname: LeMaire
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Carter
authors.forename: Ying H
authors.initials: YH
authors.lastname: Shen
authors.forename: Yehua
authors.initials: Y
authors.lastname: Gan
authors.forename: Heather
authors.initials: H
authors.lastname: Bartsch
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Wilks
authors.forename: Budi
authors.initials: B
authors.lastname: Utama
authors.forename: Hesheng
authors.initials: H
authors.lastname: Ou
authors.forename: Robert W
authors.initials: RW
authors.lastname: Thompson
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Coselli
authors.forename: Xing Li
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000368:Aged; D000784:Aortic Dissection / Q000473:pathology / Q000503:physiopathology*; D001013:Aorta, Thoracic / Q000473:pathology / Q000502:physiology; D017545:Aortic Aneurysm, Thoracic / Q000473:pathology / Q000503:physiopathology*; D004549:Elastin / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004549:Elastin