This Article Full Text Full Text (PDF) All Versions of this Article: 112/11/1601    most recent CIRCULATIONAHA.104.529537v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, L. Articles by Ruoslahti, E. Search for Related Content PubMed PubMed Citation Articles by Zhang, L. Articles by Ruoslahti, E. Pubmed/NCBI databases Substance via MeSH Related Collections Other Vascular biology Related Article

(Circulation. 2005;112:1601-1611.)
© 2005 American Heart Association, Inc.

Molecular Cardiology

Molecular Profiling of Heart Endothelial Cells

Lianglin Zhang, PhD^*; Jason A. Hoffman, PhD^*; Erkki Ruoslahti, MD, PhD

From The Cancer Research Center (L.Z., E.R.), The Burnham Institute, and the Program in Molecular Pathology (J.A.H.), The Burnham Institute, and the Department of Pathology, University of California at San Diego, School of Medicine, La Jolla, Calif.

Correspondence to Erkki Ruoslahti, Cancer Research Center, Burnham Institute, 10901 N Torrey Pines Rd, La Jolla, CA 92037. E-mail ruoslahti{at}burnham.org

Received December 13, 2004; revision received May 24, 2005; accepted May 31, 2005.

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.

Methods and 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.

---

 

CLINICAL PERSPECTIVE

Related Article:

Issue Highlights
Circulation 2005 112: 1519. [Full Text]

This article has been cited by other articles:

				P. LAAKKONEN, L. ZHANG, and E. RUOSLAHTI Peptide Targeting of Tumor Lymph Vessels Ann. N.Y. Acad. Sci., May 1, 2008; 1131(1): 37 - 43. [Abstract] [Full Text] [PDF]

				X. Sun, R. Zhang, X. Lin, and X. Xu Wnt3a Regulates the Development of Cardiac Neural Crest Cells by Modulating Expression of Cysteine-Rich Intestinal Protein 2 in Rhombomere 6 Circ. Res., April 11, 2008; 102(7): 831 - 839. [Abstract] [Full Text] [PDF]

				T. A.H. Jarvinen and E. Ruoslahti Molecular Changes in the Vasculature of Injured Tissues Am. J. Pathol., August 1, 2007; 171(2): 702 - 711. [Abstract] [Full Text] [PDF]