PLX167610

GSE111366: APOE-mediated dysfunction in human iPSC-derived endothelial cells

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Brain endothelial cells play a crucial role in the brain by forming a network of tight junctions to regulate communication between the brain and circulating factors in the blood. Various pathological conditions including cerebral atherosclerosis and stroke are associated with dysfunction of these cells. However, few in vitro models exist to directly investigate this interaction. Here, we present for the first time an in vitro model of endothelial dysfunction using isogenic human iPSC-derived cells harboring different alleles of the APOE gene, including ApoE4, a well-known genetic risk factor for cardiovascular disorders and Alzheimers disease. Using global transcriptomal analysis we found significant effects of APOE genotype on pathways involved in blood coagulation and barrier function. These were associated with functional changes in the ApoE4-expressing cells. Analysis of cytokines indicated cells harboring the ApoE4 allele are in a pro-inflammatory state, and pharmacological inhibition of inflammation reduced overexpression of the blood-clotting protein vWF. These cells therefore provide a novel model of endothelial dysfunction, and a useful platform by which to test potential therapies to improve vascular disorders. SOURCE: Jerome Feige Nestle Institute Of Health Sciences