Connective tissue changes in a mouse model of vein graft disease.
OBJECTIVE
The extracellular matrix plays an important physiological role in the architecture of the vascular wall. In arterialized vein grafts severe early changes, such as thrombosis and neointimal hyperplasia occur. Paclitaxel is in clinical use as antiproliferative coating of coronary stents. We aimed to investigate the early connective tissue changes in arterialized vein grafts and the influence of perivascular paclitaxel treatment in an in vivo model.


METHODS
C57 black mice underwent interposition of the vena cava into the carotid artery. Neointimal hyperplasia, thrombosis, acid mucopolysaccharides (Alcian), collagen fibers (trichrome Masson), elastic fibers, and apoptosis rate (TUNEL) were quantified in paclitaxel treated veins and controls.


RESULTS
In both, controls and paclitaxel treated vein grafts acid mucopolysaccharides and elastic fibers were found predominantly in the neointima, whereas collagen fibers were found mainly in the media and adventitia. At 4 weeks postoperatively the neointimal thickness in controls was 52 (13-130) microm, whereas in 0.6 mg/mL l paclitaxel treated veins it was 103 (43-318) microm (P=0.094). At 8 weeks postoperatively paclitaxel treated veins showed a significantly increased neointimal thickness of 136 (87-199) microm compared with 79 (62-146) microm in controls (P=0.032). There was no difference in apoptosis rate between the two groups (P=NS). Even with the lowest concentration of 0.008 mg/mL paclitaxel veins showed a neointimal thickness of 67 (46-205) microm at 4 weeks postoperatively (P=NS vs controls).


CONCLUSIONS
Early vein graft disease is characterised by an accumulation of acid mucopolysaccharides and elastic fibers in the thickened neointima. Paclitaxel treatment increases the neointimal hyperplasia in mouse vein grafts in vivo.
Schachner
T
T
Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria. Thomas.Schachner@uibk.ac.at
Heiss
S
S
Mayr
T
T
Steger
C
C
Zipponi
D
D
Reisinger
P
P
Bonaros
N
N
Laufer
G
G
Bonatti
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002339:Carotid Arteries / Q000601:surgery; D003094:Collagen / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000503:physiopathology; D006965:Hyperplasia; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014682:Vena Cava, Inferior / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*
D006025:Glycosaminoglycans; D003094:Collagen; D017239:Paclitaxel