Endothelial inflammation inhibitor screen

ABSTRACT: [placeholder] Endothelial inflammation is an important factor in endothelial dysfunction. TNFa and IFNg induce unique inflammation state in ECs, which is synergistically amplified when both are combined. Here we propose targeted inhibition of endothelial inflammation employing an unbiased proteomics drug inhibitor screen of NFKB and JAK/STAT targets. We show STAT6 regulates the expression of a wide range of angiogenic proteins. Inhibition of with JAK1 inhibitor itacitinib nullifies the IFNg inflammation response without off target proteomic effects. IKK2/STAT3 combined inhibition inhibited both inflammation states. Interestingly, the majority of TNFa+IFNg induced proteins could be inhibited by either JAK1 or IKK2/STAT3 inhibition, reiterating the synergetic nature of this inflammation state. Finally, we show the relation of VWF with inflammation. In conclusion we employ proteomic drug screen to assess potential drug candidates to inhibit endothelial inflammation, which highlights the feasibility of targeting the endothelium and provides an interesting outlook for future studies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Endothelial Colony Forming Cell, Vasculature

SUBMITTER: Stijn Groten  

LAB HEAD: Maartje van den Biggelaar

PROVIDER: PXD058294 | Pride | 2025-07-17

REPOSITORIES: Pride