Quantitation of cell migration in a rat carotid artery balloon injury model. Indications for a perivascular origin of the neointimal cells.
Medial and neointimal smooth muscle cells differ in phenotype. Adventitial cells have been shown to migrate to the intima and this could partly explain this difference.


OBJECTIVE
The aim of this study was to quantitate the kinetics of cell migration from the adventitial and medial layers to the intima after endothelial injury.


METHODS
Labelled proliferating cells at different periods post-injury in a rat carotid artery balloon injury model, were used to calculate the kinetics of migration using the alteration in cell populations and the ratio of proliferating cells.


RESULTS
The increase in the number of neointimal cells was greater than the level of proliferation during the 30-day follow-up. Changes in the number and percentage of proliferating cells remained low after the appearance of the first neointimal cells. 28% of the neointimal cells were labelled during the first wave of migration, and in reverse at least 72% had migrated there. Of these migrating cells, 74% were non-proliferating. The formation of neointima was efficiently blocked with cyclophosphamide and batimastat (metalloproteinase inhibitor), which resulted in a decrease in the number of medial and intimal cells.


CONCLUSIONS
The increase in the number of neointimal cells is mostly due to cells migrating from the outer layers through the media. The majority of these cells are not proliferating, but migration can still be efficiently blocked with antiproliferative drugs.
Frösen
J
J
Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Finland. jfrosen@helsinki.fi
Calderon-Ramirez
L
L
Häyry
P
P
Myllärniemi
M
M
D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology; D017539:Tunica Intima / Q000473:pathology*
D013876:Thiophenes; D010649:Phenylalanine; D003520:Cyclophosphamide; C080985:batimastat; D008666:Metalloendopeptidases