Temporal and spatial characterization of cellular constituents during neointimal hyperplasia after vascular injury: Potential contribution of bone-marrow-derived progenitors to arterial remodeling.
BACKGROUND
Exuberant smooth muscle cells (SMCs) hyperplasia is the major cause of postangioplasty restenosis. We suggested that circulating smooth muscle progenitor cells might contribute to lesion formation after vascular injury.


METHODS
We extensively investigated the cellular constituents during neointimal formation after mechanical vascular injury.


RESULTS
A large wire was inserted into the mouse femoral artery, causing complete endothelial denudation and marked enlargement of the lumen with massive apoptosis of medial SMCs. At 2 h, the injured artery remained dilated with a thin media containing very few cells. A scanning electron microscopy showed fibrin and platelet deposition at the luminal side. One week after the injury, CD45-positive hematopoietic cells accumulated at the luminal side. Those CD45-positive cells gradually disappeared, whereas neointimal hyperplasia was formed with alpha-smooth muscle actin (SMA) positive cells. Bone marrow cells and peripheral mononuclear cells differentiated into alpha-SMA-positive cells in the presence of PDGF and basic FGF. Moreover, in bone marrow chimeric mice, bone-marrow-derived cells substantially contributed to neointimal hyperplasia after wire injury.


CONCLUSIONS
These results suggest that early accumulation of hematopoietic cells may play a role in the pathogenesis of SMC hyperplasia under certain circumstances.
Shoji
Makoto
M
Third Department of Internal Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan.
Sata
Masataka
M
Fukuda
Daiju
D
Tanaka
Kimie
K
Sato
Takatoshi
T
Iso
Yoshitaka
Y
Shibata
Masayuki
M
Suzuki
Hiroshi
H
Koba
Shinji
S
Geshi
Eiichi
E
Katagiri
Takashi
T
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000648:ultrastructure*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006965:Hyperplasia; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure*; D012333:RNA, Messenger / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
D000199:Actins; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens