Decreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissection.
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.
Wang
Xinwen
X
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.
LeMaire
Scott A
SA
Chen
Li
L
Carter
Stacey A
SA
Shen
Ying H
YH
Gan
Yehua
Y
Bartsch
Heather
H
Wilks
Jonathan A
JA
Utama
Budi
B
Ou
Hesheng
H
Thompson
Robert W
RW
Coselli
Joseph S
JS
Wang
Xing Li
XL
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
D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004549:Elastin