1. Academic Validation
  2. RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease

RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease

  • Atherosclerosis. 2016 Apr;247:48-57. doi: 10.1016/j.atherosclerosis.2016.01.036.
Dean Gilham 1 Sylwia Wasiak 1 Laura M Tsujikawa 1 Christopher Halliday 1 Karen Norek 1 Reena G Patel 1 Ewelina Kulikowski 1 Jan Johansson 2 Michael Sweeney 2 Norman C W Wong 3 Allan Gordon Kevin McLure Peter Young
Affiliations

Affiliations

  • 1 Resverlogix Corp., Calgary, Canada.
  • 2 Resverlogix Corp., San Francisco, USA.
  • 3 Resverlogix Corp., Calgary, Canada. Electronic address: norm@resverlogix.com.
Abstract

High density lipoproteins (HDL), through activity of the main protein component apolipoprotein A-I (ApoA-I), can reduce the risk of Cardiovascular Disease (CVD) by removing excess Cholesterol from atherosclerotic plaque. In this study, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor RVX-208 increases ApoA-I gene transcription and protein production in human and primate primary hepatocytes. Accordingly, RVX-208 also significantly increases levels of ApoA-I, HDL-associated Cholesterol, and HDL particle number in patients who received the compound in recently completed phase 2b trials SUSTAIN and ASSURE. Moreover, a post-hoc analysis showed lower instances of major adverse cardiac events in patients receiving RVX-208. To understand the effects of RVX-208 on biological processes underlying cardiovascular risk, we performed microarray analyses of human primary hepatocytes and whole blood treated ex vivo. Overall, data showed that RVX-208 raises ApoA-I/HDL and represses pro-inflammatory, pro-atherosclerotic and pro-thrombotic pathways that can contribute to CVD risk.

Keywords

ApolipoproteinA-I; Atherosclerosis; BET bromomodomain; HDL; RVX-208.

Figures
Products