Alterations in Aortic Cellular Constituents during Thoracic Aortic Aneurysm Development

• Published in: The American journal of pathology Vol. 175; no. 4; pp. 1746 - 1756
• Main Authors: Jones, Jeffrey A, Beck, Christy, Barbour, John R, Zavadzkas, Jouzas A, Mukherjee, Rupak, Spinale, Francis G, Ikonomidis, John S
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2009
• Subjects: Pathology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.2353/ajpath.2009.081141

The present study tested the hypothesis that changes in the resident endogenous cellular population accompany alterations in aortic collagen and elastin content during thoracic aortic aneurysm (TAA) development in a murine model. Descending thoracic aortas were analyzed at various time points (2, 4, 8, and 16 weeks) post-TAA induction (0.5 M CaCl2 , 15 minutes). Aortic tissue sections were subjected to histological staining and morphometric analysis for collagen and elastin, as well as immunostaining for cell-type-specific markers to quantify fibroblasts, myofibroblasts, and smooth-muscle cells. Results were compared with reference control mice processed in the same fashion. Aortic dilatation was accompanied by changes in the elastic architecture that included: a decreased number of elastic lamellae (from 6 to 4); altered area fraction of elastin (elevated at 4 weeks and decreased at 16 weeks); and a decreased area between elastic lamellae (minimum reached at 4 weeks). Total collagen content did not change over time. Increased immunoreactivity for fibroblast and myofibroblast markers was observed at 8- and 16-week post-TAA-induction, whereas immunoreactivity for smooth-muscle cell markers peaked at 4 weeks and returned to baseline by 16 weeks. Therefore, this study demonstrated that changes in aortic elastin content were accompanied by the emergence of a subset of fibroblast-derived myofibroblasts whose altered phenotype may play a significant role in TAA development through the enhancement of extracellular matrix proteolysis.