Role of bone marrow-derived progenitor cells in cuff-induced vascular injury in mice.
OBJECTIVE
Arterial injury results in vascular remodeling associated with proliferation and migration of smooth muscle cells (SMCs) and the development of intimal hyperplasia, which is a critical component of restenosis after angioplasty of human coronary arteries and an important feature of atherosclerotic lesions. However, the origin of SMCs and other cells in the development of vascular remodeling is not yet fully understood.


RESULTS
We utilized a cuff-induced vascular injury model after transplantation of the bone marrow (BM) from green fluorescent protein (GFP)-transgenic mice. We found that macrophages were major cells recruited to the adventitia of the vascular injury lesion along with SMCs and endothelial cells (ECs). While investigating whether those cells are derived from the donor, we found that most of the macrophages were GFP-positive, and some of the SMCs and ECs were also GFP-positive. Administration of the anti-c-fms antibody resulted in a marked decrease in macrophages and a relative increase of SMCs, while administration of antibodies against the platelet-derived growth factor receptor-beta caused a prominent decrease in SMCs and a relative increase in macrophages.


CONCLUSIONS
The current study indicates that BM-derived cells play an important role in vascular injury, and that differentiation of macrophages and SMCs might be dependent on each other.
Xu
Yang
Y
Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Arai
Hidenori
H
Zhuge
Xin
X
Sano
Hideto
H
Murayama
Toshinori
T
Yoshimoto
Momoko
M
Heike
Toshio
T
Nakahata
Tatsutoshi
T
Nishikawa
Shin-ichi
S
Kita
Toru
T
Yokode
Masayuki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D003250:Constriction; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005263:Femoral Artery / Q000166:cytology / Q000293:injuries* / Q000601:surgery; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D011828:Radiation Chimera; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology; D013234:Stem Cells / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
D000911:Antibodies, Monoclonal; D049452:Green Fluorescent Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor; D020797:Receptor, Platelet-Derived Growth Factor beta