Zhang Lianglin, Hoffman Jason A, Ruoslahti Erkki
Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
Circulation. 2005 Sep 13;112(11):1601-11. doi: 10.1161/CIRCULATIONAHA.104.529537. Epub 2005 Sep 6.
Endothelial cells that line the vascular lumen can express cell-surface proteins that are specific to the endothelium of a particular tissue. In this study, we probed the heart vasculature for heart-specific endothelial markers by phage display.
We used a novel combination of in vivo phage selection and a bacterial 2-hybridization scheme against a heart cDNA library, which allows simultaneous identification of peptides that specifically bind to the target endothelium, as well as the endothelial molecules (receptors) recognized by the peptides. We found 5 heart-targeting peptides and their receptors. We confirmed and quantified the selective expression of 4 of the proteins in heart endothelial cells by independent methods. The heart specificity of phages was as high as 300-fold greater than that of nonrecombinant control phages. The proteins selectively expressed by the heart endothelium were in most cases also expressed by cardiomyocytes and, at lower levels, in some other tissues.
These findings provide new markers for the endothelium of heart vessels and reveal a commonality between parenchymal and endothelial gene expression in the heart. The heart-homing peptides provide a means of targeting diagnostic and therapeutic agents to the heart, and their receptors are potential drug discovery targets.
血管腔内的内皮细胞可表达特定组织内皮细胞特有的细胞表面蛋白。在本研究中，我们通过噬菌体展示技术在心脏血管系统中探寻心脏特异性内皮标记物。
我们采用了体内噬菌体筛选与针对心脏cDNA文库的细菌双杂交方案的新型组合，该方案能够同时鉴定特异性结合靶内皮细胞的肽段以及这些肽段所识别的内皮分子（受体）。我们发现了5种靶向心脏的肽段及其受体。我们通过独立方法证实并定量了其中4种蛋白在心脏内皮细胞中的选择性表达。噬菌体的心脏特异性比非重组对照噬菌体高300倍。心脏内皮细胞选择性表达的蛋白在大多数情况下也由心肌细胞表达，在其他一些组织中表达水平较低。
这些发现为心脏血管内皮提供了新的标记物，并揭示了心脏实质与内皮基因表达之间的共性。归巢至心脏的肽段为将诊断和治疗药物靶向输送至心脏提供了一种手段，其受体是潜在的药物发现靶点。
