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  • 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 (2016-02-13)
Dean Gilham, Sylwia Wasiak, Laura M Tsujikawa, Christopher Halliday, Karen Norek, Reena G Patel, Ewelina Kulikowski, Jan Johansson, Michael Sweeney, Norman C W Wong, Allan Gordon, Kevin McLure, Peter Young
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Goat Anti-Rabbit IgG, H & L Chain Specific Peroxidase Conjugate, liquid, Calbiochem®
Sigma-Aldrich
Apolipoprotein A-I, Human Plasma, High-Density Lipoprotein, Native apolipoprotein A-I from human plasma. Functions as a cofactor for lecithin-cholesterol acyltransferase. A component of high density lipoprotein.
Sigma-Aldrich
Goat Anti-Mouse IgG, H&L Chain Specific Peroxidase Conjugate, liquid, Calbiochem®
Sigma-Aldrich
Anti-Apolipoprotein A-I Rabbit pAb, liquid, Calbiochem®