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.
This is an author-produced, peer-reviewed version of this article. © 2009, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/). The final, definitive version of this document can be found online at The Annals of Thoracic Surgery, doi: 10.1016/j.athoracsur.2009.04.030
Complete Author List: Ioannis K. Toumpoulis, MD(Beth Israel Deaconess Medical Center); Douglas B. Cowan, PhD (Children's Hospital Julia Thom Oxford, PhD (Boise State University); Boston); Constantine E. Anagnostopoulos, MD (Columbia University College of Physicians and Surgeons); Chris K. Rokka, MD (National and Kapodistrian University of Athens); Themistocles P. Chamogeorgakis, MD (National and Kapodistrian University of Athens); Dimitrios C. Angouras, MD (National and Kapodistrian University of Athens);Richard J. Shemin, MD (Cardiovascular Center at the Ronald Reagan UCLA Medical Center); Mohamad Navab, PhD (David Geffen School of Medicine at UCLA); Maria Ericsson, BSc (Harvard Medical School); Micheline Federman, PhD (Beth Israel Deaconess Medical Center); Sidney Levitsky, MD (Beth Israel Deaconess Medical Center); and James D. McCully, PhD (Beth Israel Deaconess Medical Center).
Available at: http://works.bepress.com/julia_oxford/6/