Differential expression of collagen type V and XI alpha-1 in human ascending thoracic aortic aneurysms.
BACKGROUND
The molecular mechanisms leading to ascending thoracic aortic aneurysms (ATAAs) remain unknown. We hypothesized that alterations in expression levels of specific fibrillar collagens occur during the aneurysmal process.


METHODS
Surgical samples from ascending aortas from patients with degenerative ATAAs were subdivided by aneurysm diameter: small, 5 to 6 cm; medium, 6 to 7 cm; and large, greater than 7 cm; and compared with nonaneurysmal aortas (mean diameter, 2.3 cm).


RESULTS
Histology, immunofluorescence, and electron microscopy demonstrated greater disorganization of extracellular matrix constituents in ATAAs as compared with control with an increase in collagen alpha1(XI) within regions of cystic medial degenerative lesions. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed collagens type V and alpha1(XI) were significantly and linearly increased in ATAAs as compared with control (p < 0.001). There was no change in the messenger ribonucleic acid (mRNA) expression levels of collagens type I and III. Western blot analysis showed collagens type I and III were significantly decreased and collagens alpha1(XI) and V were significantly increased and were linearly correlated with the size of the aneurysm (p < 0.001 for both).


CONCLUSIONS
These results demonstrate that increased collagen alpha1(XI) and collagen V mRNA and protein levels are linearly correlated with the size of the aneurysm and provide a potential mechanism for the generation and progression of aneurysmal enlargement.
Toumpoulis
Ioannis K
IK
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Oxford
Julia Thom
JT
Cowan
Douglas B
DB
Anagnostopoulos
Constantine E
CE
Rokkas
Chris K
CK
Chamogeorgakis
Themistocles P
TP
Angouras
Dimitrios C
DC
Shemin
Richard J
RJ
Navab
Mohamad
M
Ericsson
Maria
M
Federman
Micheline
M
Levitsky
Sidney
S
McCully
James D
JD
D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism* / Q000503:physiopathology; D024062:Collagen Type V / Q000378:metabolism*; D024161:Collagen Type XI / Q000378:metabolism*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D024062:Collagen Type V; D024161:Collagen Type XI; D011506:Proteins; D012333:RNA, Messenger