elastin and delta-hydroxylysylnorleucine

Vein graft disease is a major and yet unsolved problem in cardiac revascularization surgery. Although accumulation of extracellular matrix is characteristic for vein graft disease, detailed analysis of the fibrotic material is lacking. Because alterations of collagen cross-links are typical for organ fibrosis, we performed a comprehensive analysis of collagen and elastin in vein graft disease.. Collagen, elastin, and their respective cross-links were analyzed using histology and amino acid analysis. The expression of collagen-modifying enzymes was analyzed using SYBR Green quantitative real-time polymerase chain reaction. Fibrillin expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction.. Diseased vein grafts showed a marked increase of collagen and of intermediate collagen cross-links, which are markers for newly synthesized collagen. Furthermore, we identified in vein graft disease increased levels of mature hydroxylysine aldehyde-derived cross-links typical for skeletal tissues. This was accompanied by upregulation of lysyl hydroxylase 2 and lysyl oxidase expression. Furthermore, vein graft disease showed a reduction of the elastin/collagen ratio, using elastin cross-links as a marker of elastin content, which was accompanied by an increase of fibrillin-1.. Vein graft disease was accompanied by marked alterations in the composition of the extracellular matrix. The altered collagen cross-link pattern and the reduced elastin/collagen ratio might synergistically increase the stiffness in diseased vein grafts. Furthermore, hydroxylysine aldehyde-derived cross-links can cause a decreased degradability of collagens by matrix-metalloproteinases. Our data suggest collagen cross-links as a therapeutic target in vein graft disease.

Topics: Aged; Case-Control Studies; Collagen; Coronary Artery Bypass; Dipeptides; Elastin; Female; Fibrillin-1; Graft Occlusion, Vascular; Humans; Male; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; Protein-Lysine 6-Oxidase; Real-Time Polymerase Chain Reaction; RNA, Messenger; Up-Regulation

Turkey poults were inoculated at hatch with the "W" isolate of Bordetella avium. At 17 d of age, serum copper levels and ceruloplasmin activities were determined. The trachea and aorta were analyzed for collagen and elastin content in an attempt to relate these structural proteins to the clinical observations of tracheal ring distortion and cardiac dysfunction associated with bordetellosis. Serum copper levels and ceruloplasmin activity were elevated in the B. avium-infected poults and indicated enzyme activity sufficient for elastin and collagen cross-link formation. In the infected poults, crude elastin content was increased significantly (0.67% infected vs 0.59% control) in the trachea but not in the aorta (13.12% infected vs 12.68% control). However, collagen content in infected poults (69.7 hydroxyproline residues per 1,000 amino acid residues) was decreased in the trachea compared to the controls (97 hydroxyproline residues per 1,000 amino acid residues), whereas collagen and elastin cross-links (HLNL, hydroxy-lysinohydroxy-norleucine, moles per mole of collagen per 300 residues hydroxyproline) were increased in the trachea of infected poults (2.85 in infected vs 1.80 in control) and also increased (DHLNL, dihydroxy-lysinohydroxy-norleucine, moles/mole of collagen/300 residues hydroxyproline) in the aorta (0.49 in infected vs 0.39 in control) of infected poults. The differences in collagen and elastin content, in association with differences in the cross-linking, appeared to be the cause of tracheal collapse that is characteristic of B. avium infection and also may have an adverse influence on cardiovascular function.

Topics: Animals; Aorta; Bordetella Infections; Ceruloplasmin; Collagen; Copper; Cross-Linking Reagents; Dipeptides; Elastin; Female; Hydroxyproline; Male; Poultry Diseases; Trachea; Tracheal Diseases; Turkeys