A biologic basis for asymmetric growth in descending thoracic aortic aneurysms: a role for matrix metalloproteinase 9 and 2.
OBJECTIVE
This study was undertaken to define matrix metalloproteinase (MMP) expression in the anterior and posterior wall of descending thoracic aortic aneurysms (TAAs) and correlate it with specific computed tomography (CT) image sites within the descending thoracic aorta.


METHODS
Serial CT images of patients with TAAs were compared with age- and gender-matched normal descending thoracic aortas at levels T4-T12. The mean circumference of the TAAs was 153 mm (n = 12) and 148 mm (n = 11) at T8 and T10, respectively, compared with 75 mm (n = 12) and 75 mm (n = 10) in controls (P < .001). Aortic tissue was collected from a separate set of eight patients undergoing descending TAA resection (processed < or =12 hours of excision) and six cadavers (processed < or =24 hours of death). Tissue collected between the intercostals arteries was defined as posterior wall, and directly opposite was the anterior wall. MMP-9 and MMP-2 messenger RNA (mRNA) extracted from aortic tissue was analyzed by quantitative real time polymerase chain reaction (PCR) and normalized to beta-actin. Immunohistochemistry was performed for MMP-9 and MMP-2. CT aortic measurements and MMP expression were compared by t tests and analysis of variance, respectively.


RESULTS
The ratio of arc distance between the intercostals on the posterior wall to total aortic circumference was 0.14 in healthy controls compared with 0.08 in TAAs at vertebral level T8 (P = .001). At T10, the ratio was 0.15 in healthy controls compared with 0.11 in TAAs (P = .001). MMP-9 expression in TAAs was 4.3-fold higher in the anterior wall compared with the posterior wall (P = .03). Conversely, MMP-2 expression in TAAs was 3.2-fold higher in the posterior wall compared with the anterior wall (P = .008). MMP expression was not detected in control cadaver aortas.


CONCLUSIONS
Anterior walls of expanding TAAs grow at a greater rate than the posterior wall, as determined from the lower ratio of intercostal arc distance to total circumference in TAAs. Differential MMP expression appears to be a biologic marker for asymmetric growth in the TAA wall.


CONCLUSIONS
The pathogenesis of thoracic aortic aneurysms (TAAs) is poorly understood. Multiple lines of evidence suggest that matrix metalloproteinases (MMPs), a family of enzymes, are important in aneurysm development. Earlier experiments documented a regional variation of MMP-9 in stimulated rodent aortas, with production greater in the abdominal aorta compared with the thoracic aorta. The present study extends that observation and documents asymmetric aneurysm development in the TAA wall, with increased anterior wall growth in correlation to increased MMP-9 production. An improved understanding of the mechanisms by which MMP production is regulated is critical.
Sinha
Indranil
I
Section of Vascular Surgery, University of Michigan, Ann Arbor, MI 48109-0329, USA.
Bethi
Siddharth
S
Cronin
Paul
P
Williams
David M
DM
Roelofs
Karen
K
Ailawadi
Gorav
G
Henke
Peter K
PK
Eagleton
Matthew J
MJ
Deeb
G Michael
GM
Patel
Himanshu J
HJ
Berguer
Ramon
R
Stanley
James C
JC
Upchurch
Gilbert R
GR
D017545:Aortic Aneurysm, Thoracic / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D004108:Dilatation, Pathologic; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D014057:Tomography, X-Ray Computed
D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9