Can I read So078apabetalone, A Bromodomain And Extra-terminal (bet) Protein Inhibitor, Reduces Alkaline Phosphatase In Cvd Patients, In Mice, And In Cell Culture Systems on EtoBox?

So078apabetalone, A Bromodomain And Extra-terminal (bet) Protein Inhibitor, Reduces Alkaline Phosphatase In Cvd Patients, In Mice, And In Cell Culture Systems by Dean Gilham; Laura Tsujikawa; Sylwia Wasiak; Ravi Jahagirdar; Li Fu; Phoebe Ho; Christopher Halliday; Christopher Sarsons; Stephanie Stotz; Brooke Rakai; Kenith Lebioda; Jan Johansson; Michael Sweeney; Norman Wong; Kamyar Kalantar-Zadeh; Mathias Haarhaus; Ewelina Kulikowski is a Medicine article available to read on EtoBox.

What is So078apabetalone, A Bromodomain And Extra-terminal (bet) Protein Inhibitor, Reduces Alkaline Phosphatase In Cvd Patients, In Mice, And In Cell Culture Systems about?

## Abstract ## Background and Aims Elevated serum alkaline phosphatase (ALP) independently predicts major adverse cardiac events (MACE) by contributing to vascular calcification and endothelial dysfunction arising in chronic kidney disease (CKD) and cardiovascular disease (CVD). Apabetalone is an orally active inhibitor of bromodomain and extraterminal (BET) proteins – epigenetic readers that modulate gene expression involved in vascular inflammation and calcification. Here we examined apabetalone’s effects on ALP post-hoc in recent clinical trials, then performed mechanistic studies into apabetalone’s impact on tissue non-specific ALP (TNALP) expression in mice and cell culture. ## Method Serum ALP was determined in CVD patients in phase 2 trials (3 month ASSERT and 6 month SUSTAIN & ASSURE) and in the phase 3 BETonMACE CVD outcomes trial, including subpopulations with CKD (eGFR<60 mL/min/1.73m2). Apabetalone’s effect on expression of TNALP (gene symbol ALPL) was examined in mice, cultured primary human hepatocytes (PHH), HepaRG, HepG2, vascular smooth muscle cells (VSMCs), and vascular endothelial cells by real-time PCR. TNALP protein levels were assessed by immunoblots and flow

Who reads So078apabetalone, A Bromodomain And Extra-terminal (bet) Protein Inhibitor, Reduces Alkaline Phosphatase In Cvd Patients, In Mice, And In Cell Culture Systems?

Author

Dean Gilham; Laura Tsujikawa; Sylwia Wasiak; Ravi Jahagirdar; Li Fu; Phoebe Ho; Christopher Halliday; Christopher Sarsons; Stephanie Stotz; Brooke Rakai; Kenith Lebioda; Jan Johansson; Michael Sweeney; Norman Wong; Kamyar Kalantar-Zadeh; Mathias Haarhaus; Ewelina Kulikowski

Publisher

Oxford University Press; Oxford University Press (OUP) (ISSN 0931-0509)

Published

2020

Language

EN

Field

Medicine (Health Sciences)