Hao Hiroyuki, Hirota Seiichi, Ishibashi-Ueda Hatsue, Kushiro Toshio, Kanmatsuse Katsuo, Yutani Chikao
Department of Pathology, National Cardiovascular Center, Suita, Osaka, Japan.
Cardiovasc Pathol. 2004 Jul-Aug;13(4):195-202. doi: 10.1016/j.carpath.2004.03.607.
Recent data indicate that matrix proteins such as matrix Gla protein (MGP) and osteonectin (ON) influence not only mineralization of vasculature but smooth muscle cell (SMC) differentiation.
We examined whether MGP and ON are expressed by human aortic SMCs in vivo using Northern blotting, in situ hybridization and immunohistochemistry.
MGP and ON mRNAs were strongly expressed in the aorta without atherosclerosis from newborn and four young subjects up to 10 years old. In the aorta from 15 adult cases, MGP and ON mRNAs were decreased as atherosclerosis developed. We determined cell type and distribution of the MGP- and ON mRNA-expressing cells by in situ hybridization and immunohistochemistry. In the aorta obtained from newborn and young subjects, SMCs in the media and thin intima expressed MGP mRNA and, to a lesser extent, ON mRNA. In the adult aorta with fibrous thickening, MGP mRNA was expressed by intimal SMCs and subpopulation of medial SMCs. Osteonectin mRNA was expressed mainly by intimal SMCs and few medial SMCs. Double immunohistochemical staining revealed that both MGP- and ON protein-expressing cells were positive for anti-alpha-smooth muscle actin antibody, aortic SMCs.
These results suggested that MGP and ON expression by aortic SMCs might be regulated by the degree of atherosclerosis and SMC differentiation in human aorta.
近期数据表明,诸如基质γ-羧基谷氨酸蛋白(MGP)和骨连接蛋白(ON)等基质蛋白不仅影响脉管系统的矿化,还影响平滑肌细胞(SMC)的分化。
我们使用Northern印迹法、原位杂交和免疫组织化学检测了人主动脉平滑肌细胞在体内是否表达MGP和ON。
在来自新生儿和4名10岁以下年轻受试者的无动脉粥样硬化的主动脉中,MGP和ON mRNA强烈表达。在15例成人的主动脉中,随着动脉粥样硬化的发展,MGP和ON mRNA减少。我们通过原位杂交和免疫组织化学确定了表达MGP和ON mRNA的细胞类型和分布。在从新生儿和年轻受试者获得的主动脉中,中膜和薄内膜中的平滑肌细胞表达MGP mRNA,在较小程度上表达ON mRNA。在有纤维增厚的成人主动脉中,内膜平滑肌细胞和中膜平滑肌细胞亚群表达MGP mRNA。骨连接蛋白mRNA主要由内膜平滑肌细胞和少数中膜平滑肌细胞表达。双重免疫组织化学染色显示,表达MGP和ON蛋白的细胞均对抗α-平滑肌肌动蛋白抗体呈阳性,即主动脉平滑肌细胞。
这些结果表明,人主动脉中平滑肌细胞的MGP和ON表达可能受动脉粥样硬化程度和平滑肌细胞分化的调节。