Molecular profiling of heart endothelial cells.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Zhang
Lianglin
L
Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
Hoffman
Jason A
JA
Ruoslahti
Erkki
E
D000818:Animals; D001435:Bacteriophages; D015415:Biomarkers / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D007275:Injections, Intravenous; D060588:LIM Domain Proteins; D008024:Ligands; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
D015415:Biomarkers; D002352:Carrier Proteins; C507808:Crip2 protein, mouse; D060588:LIM Domain Proteins; D008024:Ligands; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C507807:cysteinyl-arginyl-prolyl-prolyl-arginine