Discovery approaches to UPR in athero-susceptible endothelium in vivo.

The endothelium is a monolayer of cells that lines the entire inner surface of the cardiovascular and lymphatic circulations where it controls normal physiological functions through both systemic and local regulation. Endothelial phenotypes are heterogeneous, dynamic and malleable, properties that in large- and medium-sized arteries lead to a central role in the development of focal and regional atherosclerosis. The endothelial phenotype in athero-susceptible sites is different from that in nearby athero-resistant regions. Understanding the in vivo gene, protein, and metabolic expression profiles of susceptible endothelium is, therefore, an important spatiotemporal challenge in atherosclerosis research. Recent studies have demonstrated that endoplasmic reticulum (ER) stress and the UPR are characteristics of susceptible endothelium. Here, we outline global genomic profiling, pathway analyses, and gene connectivity approaches to the identification of UPR and associated pathways as discrete markers of athero-susceptibility in arterial endothelium.