Xu Yang, Arai Hidenori, Zhuge Xin, Sano Hideto, Murayama Toshinori, Yoshimoto Momoko, Heike Toshio, Nakahata Tatsutoshi, Nishikawa Shin-ichi, Kita Toru, Yokode Masayuki
Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):477-82. doi: 10.1161/01.ATV.0000118016.94368.35. Epub 2004 Jan 22.
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.
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.
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.
动脉损伤会导致血管重塑，这与平滑肌细胞（SMC）的增殖和迁移以及内膜增生的发展相关，内膜增生是人类冠状动脉血管成形术后再狭窄的关键组成部分，也是动脉粥样硬化病变的一个重要特征。然而，血管重塑过程中SMC及其他细胞的来源尚未完全明确。
我们利用了一种在移植来自绿色荧光蛋白（GFP）转基因小鼠的骨髓（BM）后通过袖带诱导的血管损伤模型。我们发现巨噬细胞是与SMC和内皮细胞（EC）一起被招募到血管损伤病变外膜的主要细胞。在研究这些细胞是否来源于供体时，我们发现大多数巨噬细胞是GFP阳性的，并且一些SMC和EC也是GFP阳性的。给予抗c-fms抗体导致巨噬细胞显著减少，SMC相对增加，而给予抗血小板衍生生长因子受体-β抗体则导致SMC显著减少，巨噬细胞相对增加。
当前研究表明骨髓来源的细胞在血管损伤中起重要作用，并且巨噬细胞和SMC的分化可能相互依赖。
