Matrix metalloproteinases in ascending aortic aneurysms: bicuspid versus trileaflet aortic valves.
BACKGROUND
Abnormal matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) expression contributes to the development of abdominal aortic aneurysms. Recent data suggest that MMP-2 and MMP-9 may also play a role in thoracic aortic disease. We sought to determine (1) whether ascending aortic aneurysms are associated with increased MMP expression and (2) whether aortic inflammation and MMP expression differ between patients with congenital bicuspid aortic valves (BAVs) and those with trileaflet aortic valves (TAVs).


METHODS
Samples of ascending aortic aneurysms were obtained from 29 patients; 14 patients had BAVs and 15 had TAVs. Control ascending aorta was obtained from 14 organ donors or heart transplant recipients. Aortic histology and immunohistochemistry were performed to evaluate elastin degradation, inflammatory changes, and MMP-2 and MMP-9 expression. Aortic levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured using ELISA.


RESULTS
Aneurysms in the TAV patients exhibited marked inflammation, high CD68 expression, diminished elastin content, increased MMP-9 expression, and normal MMP-2 levels. In contrast, BAV aneurysms were characterized by a relative lack of inflammation, preservation of elastin content, normal MMP-9 levels, and elevated MMP-2 expression. TIMP-1 and TIMP-2 levels were not significantly different among the three groups.


CONCLUSIONS
Ascending aortic aneurysms exhibited increased MMP expression. The pattern of MMP expression and the degree of inflammation, however, differed between aneurysms associated with BAVs and those with TAVs. Variations in the molecular mechanisms underlying different types of thoracic aortic aneurysms warrant further investigation.
LeMaire
Scott A
SA
Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine and The Methodist DeBakey Heart Center, Houston, Texas, USA. slemaire@bcm.tmc.edu
Wang
Xinwen
X
Wilks
Jonathan A
JA
Carter
Stacey A
SA
Wen
Shixiang
S
Won
Taehee
T
Leonardelli
Dominic
D
Anand
Gobind
G
Conklin
Lori D
LD
Wang
Xing Li
XL
Thompson
Robert W
RW
Coselli
Joseph S
JS
D000328:Adult; D001014:Aortic Aneurysm / Q000201:enzymology* / Q000473:pathology; D001021:Aortic Valve / Q000002:abnormalities*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases