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-1 in Human Ascending Thoracic Aortic Aneurysms
a Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts
b Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
c Department of Anesthesiology, Children's Hospital Boston, Boston, Massachusetts
d Electron Microscopy Core Facility, Harvard Medical School, Boston, Massachusetts
e Department of Biology, Biomolecular Research Center, Boise State University, Boise, Idaho
f Department of Cardiothoracic Surgery, St. Luke's – Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York
g Department of Cardiothoracic Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
h Division of Cardiothoracic Surgery, Cardiovascular Center at the Ronald Reagan UCLA Medical Center, Los Angeles, California
i Department of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, California
Accepted for publication April 9, 2009.
* Address correspondence to Dr McCully, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Room 144, Boston, MA 02115 (Email: james_mccully{at}hms.harvard.edu).
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
1(XI) within regions of cystic medial degenerative lesions. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed collagens type V and
1(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
1(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
1(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.
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A. Nsair and K. Schenke-Layland Invited commentary. Ann. Thorac. Surg., August 1, 2009; 88(2): 513 - 514. [Full Text] [PDF] |
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