title: Morphological changes of the aortic valve leaflets in non-compliant aortic roots: in-vivo experiments.
abstract: OBJECTIVE
  Age-related loss of elasticity of the naturally compliant aortic root disrupts the coordinated function of the valve leaflets. Morphological changes that developed over time in the aortic valve leaflets of non-compliant aortic roots were studied.
  
  
  METHODS
  Stiffening of the aortic roots was achieved in vivo by applying Super Glue around the sinus of Valsalva in 27 New Zealand White rabbits. In nine animals, glue was applied only partially, and eight untreated rabbits served as controls. Histological evaluation of the aortic valves was performed at 8-11 months after surgery, and included immunohistochemistry and confocal microscopy with quantitative tissue assessment. Levels of collagen I, as a main component of fibrosis, and matrix metalloproteinases (MMP)-1 and MMP-9 and angiotensin-converting enzyme (ACE), as regulators of fibrosis, were analyzed. The morphological structure of the aortic valve leaflets was studied, and the length, thickness and area of leaflets were measured.
  
  
  RESULTS
  Leaflects in all groups were found to be composed of a continuous layer of collagen fibers at the mural side, and loose connective tissue containing fibroblasts and few capillaries on the aortic luminal aspect. In stiffened aortic roots, the length and area of the leaflets were increased. The area occupied by collagen was elevated in non-compliant aortic root leaflets, but collagen fluorescence intensity was decreased, indicating less densely packed collagen fibers. Degradation and synthesis of collagen as reflected by MMP-1, MMP-9 and ACE levels was up-regulated.
  
  
  CONCLUSIONS
  Loss of compliance in aortic roots leads to elongation of the leaflets which, combined with a decrease in collagen density, may render leaflets more susceptible to mechanical stress. In time, this may promote the development of degenerative changes in the aortic valve.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Heineman Medical Research Laboratories, Carolinas Medical Center, 1000 Blythe Blvd., Charlotte, NC 28203, USA. tjohn@sanger-clinic.com
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Fokin
authors.forename: Francis
authors.initials: F
authors.lastname: Robicsek
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Cook
authors.forename: Mano J
authors.initials: MJ
authors.lastname: Thubrikar
authors.forename: Jutta
authors.initials: J
authors.lastname: Schaper
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D001018:Aortic Diseases / Q000150:complications*; D001021:Aortic Valve / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004548:Elasticity; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011817:Rabbits; D012850:Sinus of Valsalva / Q000503:physiopathology*
chemical_list: D007703:Peptidyl-Dipeptidase A; D020782:Matrix Metalloproteinases