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Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
Molecular profiling of heart endothelial cells
Lianglin Zhang1, Jason A Hoffman, Erkki Ruoslahti
1Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA.
Insights
Researchers identified novel heart-specific endothelial markers using phage display. These findings offer new diagnostic and therapeutic targets for heart conditions, advancing cardiovascular research.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Biotechnology
Background:
- Endothelial cells lining blood vessels can exhibit tissue-specific cell-surface proteins.
- Identifying these unique markers is crucial for understanding tissue-specific biology and developing targeted therapies.
Purpose of the Study:
- To discover novel, heart-specific endothelial markers.
- To identify peptides that specifically target heart vasculature and their corresponding endothelial receptors.
Main Methods:
- Employed a novel combination of in vivo phage selection and bacterial 2-hybridization.
- Utilized a heart cDNA library for simultaneous identification of targeting peptides and their receptors.
- Confirmed and quantified selective protein expression in heart endothelial cells using independent methods.
Main Results:
- Identified 5 heart-targeting peptides and their corresponding receptors.
- Confirmed selective expression of 4 proteins in heart endothelial cells, with up to 300-fold greater specificity compared to controls.
- Observed that identified proteins were also expressed in cardiomyocytes and other tissues at lower levels.
Conclusions:
- Discovery of new markers for heart vessel endothelium.
- Revealed shared gene expression patterns between heart parenchyma and endothelium.
- Heart-homing peptides and their receptors represent potential targets for diagnostic/therapeutic agents and drug discovery.
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.
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