Apoptosis signal-regulating kinase 1 inhibition reverses deleterious indoxyl sulfate-mediated endothelial effects
Feby Savira, Andrew R Kompa, Ruth Magaye, Xin Xiong, Li Huang, Beat M Jucker, Robert N Willette, Darren J Kelly, Bing H Wang
Life Sciences | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2021
AIMS: Indoxyl sulfate (IS), a protein-bound uremic toxin, is implicated in endothelial dysfunction, which contributes to adverse cardiovascular events in chronic kidney disease. Apoptosis signal regulating kinase 1 (ASK1) is a reactive oxygen species-driven kinase involved in IS-mediated adverse effects. This study assessed the therapeutic potential of ASK1 inhibition in alleviating endothelial effects induced by IS. MAIN METHODS: IS, in the presence and absence of a selective ASK1 inhibitor (GSK2261818A), was assessed for its effect on vascular reactivity in rat aortic rings, and cultured human aortic endothelial cells where we evaluated phenotypic and mechanistic changes. KEY FINDINGS: IS ..View full abstract
Awarded by National Health and Medical Research Council of Australia
This research was supported by National Health and Medical Research Council of Australia (Program Grant #1092642 and Project Grant #1087355).