Differential Expression of Collagen Type V and XI α-1 in Human Ascending Thoracic Aortic Aneurysms

• Published in: The Annals of thoracic surgery Vol. 88; no. 2; pp. 506 - 513
• Main Authors: Toumpoulis, Ioannis K., MD, Oxford, Julia Thom, PhD, Cowan, Douglas B., PhD, Anagnostopoulos, Constantine E., MD, Rokkas, Chris K., MD, Chamogeorgakis, Themistocles P., MD, Angouras, Dimitrios C., MD, Shemin, Richard J., MD, Navab, Mohamad, PhD, Ericsson, Maria, BSc, Federman, Micheline, PhD, Levitsky, Sidney, MD, McCully, James D., PhD
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.08.2009
• Subjects: Aortic Aneurysm, Thoracic - metabolism; Aortic Aneurysm, Thoracic - physiopathology; Cardiothoracic Surgery; Collagen Type V - metabolism; Collagen Type XI - metabolism; Disease Progression; Extracellular Matrix - pathology; Humans; Immunohistochemistry; Proteins - analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Surgery; 26
• ISSN: 0003-4975; 1552-6259
• DOI: 10.1016/j.athoracsur.2009.04.030

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 α1(XI) within regions of cystic medial degenerative lesions. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed collagens type V and α1(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 α1(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 α1(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.