Endothelial heterogeneity associated with regional athero-susceptibility and adaptation to disturbed blood flow in vivo.
Endothelial phenotypic heterogeneity plays an important role in the susceptibility of the cardiovascular system to disease. Arteries and heart valves are susceptible to chronic inflammatory disease in regions of blood flow disturbance that implicates hemodynamic forces and transport characteristics as prominent influences on endothelial phenotype. By combining in vivo high-throughput genomics (discovery science) and in vitro mechanistic approaches (reductionist science), we present endothelial patho-susceptibility as an imbalance of multiple interrelated pathways that sensitize the cells to pathological change. The recently identified association of endoplasmic reticulum stress with endothelium in regions of flow disturbance is outlined as an important example of susceptible phenotype linked to proinflammatory and oxidative stress pathways.
Davies
Peter F
PF
Institute for Medicine and Engineering, Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. pfd@pobox.upenn.edu
Civelek
Mete
M
Fang
Yun
Y
Guerraty
Marie A
MA
Passerini
Anthony G
AG
D000222:Adaptation, Physiological; D000818:Animals; D001158:Arteries / Q000473:pathology*; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D004198:Disease Susceptibility; D004721:Endoplasmic Reticulum / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D020869:Gene Expression Profiling; D018056:Hemorheology; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D033081:Shear Strength; D013552:Swine; D056811:Unfolded Protein Response; D014657:Vasculitis / Q000473:pathology / Q000503:physiopathology
D016328:NF-kappa B