Zhao Xue, Johnson Jennifer N, Singh Krishna, Singh Mahipal
Department of Physiology, James H. Quillen College of Medicine, James H. Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, Tennessee 37614, USA.
Microcirculation. 2007 Apr-May;14(3):233-40. doi: 10.1080/10739680601139369.
Osteopontin (OPN), increased in the heart following myocardial infarction (MI), plays an important role in post-MI remodeling. Angiogenesis, an important feature of tissue repair, begins in the infarcted myocardium within 3 days post-MI. Here, the authors studied the role of OPN in myocardial angiogenesis using wild-type (WT) and OPN knockout (KO) mice.
Measurement of angiogenic response using Griffonia simplicifolia lectin-1 (GSL-1) staining indicated reduced capillary density in the infarcted region of the OPN KO hearts as compared to WT hearts 7 and 14 days post-MI. Arteriolar density was lower in OPN KO hearts 14 days post-MI. The number of CD31 positive cells was also lower in the infarcted region of the OPN KO hearts as compared to WT hearts 14 days post-MI. In contrast, capillary and arteriolar densities in the noninfarcted regions of OPN KO and WT hearts were not significantly different. In vivo myocardial angiogenesis measured using Matrigel implantation in the left ventricular myocardium indicated significant decrease in the percentage of vessel-like areas in the OPN KO vs. WT hearts. Furthermore, in vitro Matrigel tube formation assay demonstrated a significant decrease in total tube length in cardiac microvascular endothelial cells (CMECs) isolated from OPN KO hearts as compared to CMECs from WT hearts. Treatment of OPN KO CMECs with purified OPN protein significantly increased total tube length, while bovine serum albumin had no effect.
Lack of OPN impairs myocardial angiogenic response, leading to adverse remodeling post-MI.
骨桥蛋白（OPN）在心肌梗死后心脏中表达增加，在心肌梗死后重塑过程中起重要作用。血管生成是组织修复的一个重要特征，在心肌梗死后3天内在梗死心肌中开始。在此，作者使用野生型（WT）和OPN基因敲除（KO）小鼠研究了OPN在心肌血管生成中的作用。
使用四豆凝集素-1（GSL-1）染色测量血管生成反应表明，与心肌梗死后7天和14天的野生型心脏相比，OPN基因敲除心脏梗死区域的毛细血管密度降低。心肌梗死后14天，OPN基因敲除心脏的小动脉密度较低。与心肌梗死后14天的野生型心脏相比，OPN基因敲除心脏梗死区域的CD31阳性细胞数量也较少。相比之下，OPN基因敲除和野生型心脏非梗死区域的毛细血管和小动脉密度没有显著差异。使用基质胶植入左心室心肌测量的体内心肌血管生成表明，与野生型心脏相比，OPN基因敲除心脏中血管样区域的百分比显著降低。此外，体外基质胶管形成试验表明，与野生型心脏分离的心脏微血管内皮细胞（CMECs）相比，OPN基因敲除心脏分离的CMECs的总管长度显著降低。用纯化的OPN蛋白处理OPN基因敲除的CMECs可显著增加总管长度，而牛血清白蛋白则无作用。
缺乏OPN会损害心肌血管生成反应，导致心肌梗死后不良重塑。
