Beta-galactosidase-tagged adventitial myofibroblasts tracked to the neointima in healing rat vein grafts.
OBJECTIVE
Myofibroblasts are present transiently in normal healing wounds. However, they have been found to persist in the stroma of neoplasms, fibrotic conditions and other pathological settings. In rat vein grafts, we have observed the prolonged presence of myofibroblasts. Our aim was to determine the origin of myofibroblasts in vein grafts.


METHODS
Epigastric vein to femoral artery grafts were microsurgically placed in male Lewis rats and harvested. Neointimal development, cellular death and proliferation, and cell phenotypes were analyzed using immunohistochemistry and light and electron microscopy. To follow cellular movement in the vessel wall, vein grafts were transfected with replication-defective adenovirus containing the gene encoding beta-galactosidase (n = 50), and harvested at 1, 2, 3, 4, 5, 6, 7, 14 and 28 days. Grafts were analyzed after X-gal staining.


RESULTS
Myofibroblasts were detected in the outer adventitia at 4 days, in the media at 1 week and in the developing neointima at 2 weeks. Cells tagged using adenoviral beta-galactosidase demonstrated adventitia to neointima cell migration.


CONCLUSIONS
Although there may be other sources of myofibroblasts in this model, the adventitia has been shown to be an origin of myofibroblasts which subsequently migrate through the vessel wall to the neointima during graft remodeling and contribute to neointimal formation.
Tomas
Jeffrey J
JJ
Department of Surgery, University of Wisconsin School of Medicine, Madison, Wisconsin 53792, USA.
Stark
V Emily
VE
Kim
Jimmy L
JL
Wolff
Randal A
RA
Hullett
Debra A
DA
Warner
Thomas F
TF
Hoch
John R
JR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D003239:Connective Tissue Cells / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005263:Femoral Artery / Q000601:surgery; D005347:Fibroblasts / Q000502:physiology*; D005822:Genetic Vectors; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D014162:Transfection; D017539:Tunica Intima / Q000473:pathology / Q000502:physiology*; D014680:Veins / Q000601:surgery; D014945:Wound Healing / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics
D003598:Cytoskeletal Proteins; D001616:beta-Galactosidase