Apoptosis signal-regulating kinase 1 inhibition attenuates cardiac hypertrophy and cardiorenal fibrosis induced by uremic toxins: Implications for cardiorenal syndrome.

ABSTRACT: Intracellular accumulation of protein-bound uremic toxins in the setting of cardiorenal syndrome leads to adverse effects on cardiorenal cellular functions, where cardiac hypertrophy and cardiorenal fibrosis are the hallmarks. In this study, we sought to determine if Apoptosis Signal-Regulated Kinase 1 (ASK1), an upstream regulator of cellular stress response, mediates cardiac hypertrophy and cardiorenal fibrosis induced by indoxyl sulfate (IS) and p-cresol sulfate (PCS) in vitro, and whether ASK1 inhibition is beneficial to ameliorate these cellular effects. PCS augmented cardiac myocyte hypertrophy and fibroblast collagen synthesis (as determined by 3H-leucine and 3H-proline incorporation, respectively), similar to our previous finding with IS. IS and PCS also increased collagen synthesi

SUBMITTER: Savira F 

PROVIDER: S-EPMC5673193 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature