Possible vascular drug targets and biomarkers mapped
Endothelial cells line the inside of all blood vessels and regulate inflammation, blood clotting following injury and blood pressure levels. These specialised processes involve proteins that are mainly expressed in this particular cell type throughout the body, which are often modulated in vascular disease. Identification of such endothelial-enriched proteins is difficult, as their expression can be quickly changed once the cells are removed from the body to study; thus, only a limited number of such proteins are currently described.
Researchers from KTH Royal Institute of Technology, Karolinska Institutet and University Medical Centre Hamburg-Eppendorf, in collaboration with the Human Protein Atlas Project, worked with a systems-based approach to identify a large panel of genes predominantly expressed in human endothelial cells. They used a method to identify genes that are co-expressed with already known endothelial-enriched genes and analysed RNA sequencing data from 124 unprocessed tissue samples from 32 different organs. Tissue staining was used to confirm the findings.
In total 234 cell-specific genes were identified, 118 of which encode for novel or uncharacterised endothelial proteins. Amongst these were genes that were lost when endothelial cells were removed from the body and cultured in the laboratory, which potentially explains the previous failure to identify them. A searchable resource that can be used to determine how ‘endothelial-specific’ any protein is can be downloaded from the publication.
This study, published in Cell Systems, reveals new vascular drug targets and potential biomarkers of vascular disease. In addition it provides a platform from which to increase our understanding of the vasculature, through the investigation of the function of the unknown genes –which are likely to have a role in the specilised function of the endothelium.
The study was led by Lynn Butler, University Medical Centre Hamburg/Karolinska Institutet together with Jacob Odeberg KTH Royal Institute of Technology/SciLifeLab. Fredrik Pontén, Uppsala Universitet/SciLifeLab and Mathias Uhlén, KTH Institute of Technology/SciLifeLab also contributed to the article.