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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:477.)
© 2004 American Heart Association, Inc.

Vascular Biology

Role of Bone Marrow–Derived Progenitor Cells in Cuff-Induced Vascular Injury in Mice

Yang Xu; Hidenori Arai; Xin Zhuge; Hideto Sano; Toshinori Murayama; Momoko Yoshimoto; Toshio Heike; Tatsutoshi Nakahata; Shin-ichi Nishikawa; Toru Kita; Masayuki Yokode

From the Departments of Geriatric Medicine (H.S.), Pediatrics (M. Yoshimoto, T.H., T.N.), and Cardiovascular Medicine (T.K.), Kyoto University Graduate School of Medicine, Japan; the Translational Research Center (Y.X., X.Z., T.M., M. Yokode), Kyoto University Hospital, Kyoto, Japan; and the RIKEN Center for Developmental Biology (S.N.), Kobe, Japan

Correspondence to Hidenori Arai, MD, PhD, Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. E-mail harai{at}kuhp.kyoto-u.ac.jp

Objectives— 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.

Methods and 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-ß 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.

Key Words: macrophage • smooth muscle cell • endothelial cell • vascular injury • bone marrow

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