title: Alterations in aortic cellular constituents during thoracic aortic aneurysm development: myofibroblast-mediated vascular remodeling.
abstract: 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.
authors.affiliation: Division of Cardiothoracic Surgery Research, Department of Surgery, Medical University of South Carolina, Strom Thurmond Research Building, 114 Doughty Street, Suite 625, Charleston, SC 29425, USA. jonesja@musc.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jones
authors.forename: Christy
authors.initials: C
authors.lastname: Beck
authors.forename: John R
authors.initials: JR
authors.lastname: Barbour
authors.forename: Jouzas A
authors.initials: JA
authors.lastname: Zavadzkas
authors.forename: Rupak
authors.initials: R
authors.lastname: Mukherjee
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
authors.forename: John S
authors.initials: JS
authors.lastname: Ikonomidis
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology*; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity
chemical_list: D003094:Collagen; D004549:Elastin