Vascular cell kinetics in response to intimal injury ex vivo.
BACKGROUND
Recent studies indicate that the smooth muscle-like cells contributing to neointimal hyperplasia after vascular injury derive from circulating precursor cells. Here, we define the time course of precursor cell influx, the roles of separate vascular layers, and the relative role of migration versus proliferation to intimal hyperplasia.


RESULTS
After rat aortic denudation injury the neointimal cell number increased several 100-fold between days 4 and 28, preceded by a 5-fold increase in the number of adventitial cells and a 4-fold increase in the number of adventitial microvessels. The influx, migration, and maturation of neointimal cells were quantitated by culturing whole vessel explants at different time points after injury. Explant outgrowth increased 14-fold, and cell migration 3.5-fold on days 2-14 after injury. Cell proliferation increased less than 2-fold. The frequency of precursors to outgrowing cells, determined using limiting dilution analysis, increased 8-fold between days 2 and 4 after injury. Many outgrowing cells displayed characteristics of undifferentiated cells.


CONCLUSIONS
Adventitial activation precedes development of the neointima, and precursor cell influx occurs on days 2-14 after injury. Cell migration, more than proliferation, contributes to fibrointimal dysplasia. These findings underline the importance of early therapeutic intervention with antimigratory compounds to prevent neointimal hyperplasia.
Tigerstedt
Nina-Maria
NM
Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. nina-maria.tigerstedt@helsinki.fi
Savolainen-Peltonen
Hanna
H
Lehti
Satu
S
Hayry
Pekka
P
D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D003238:Connective Tissue / Q000098:blood supply; D006965:Hyperplasia; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D055806:Microvessels / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D009924:Organ Culture Techniques; D051381:Rats; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism / Q000473:pathology*
D015415:Biomarkers