Data on gene and protein expression changes induced by apabetalone (RVX-208) in ex vivo treated human whole blood and primary hepatocytes

Abstract

Apabetalone (RVX-208) inhibits the interaction between epigenetic regulators known as bromodomain and extraterminal (BET) proteins and acetyl-lysine marks on histone tails. Data presented here supports the manuscript published in Atherosclerosis "RVX-208, a BET-inhibitor for Treating Atherosclerotic Cardiovascular Disease, Raises ApoA-I/HDL and Represses Pathways that Contribute to Cardiovascular Disease" (Gilham et al., 2016) [1]. It shows that RVX-208 and a comparator BET inhibitor (BETi) JQ1 increase mRNA expression and production of apolipoprotein A-I (ApoA-I), the main protein component of high density lipoproteins, in primary human and African green monkey hepatocytes. In addition, reported here are gene expression changes from a microarray-based analysis of human whole blood and of primary human hepatocytes treated with RVX-208.

Keywords: African green monkey; ApoA-I; Apolipoprotein A-I; BET inhibitor; BET proteins; Bromodomain; Gene expression; JQ1; Microarrays; Primary human hepatocytes; RVX-208; Vascular inflammation.

Fig. 1

Effect of RVX-208 on ApoA-I mRNA expression in African green monkey hepatocytes. Hepatocyte 3-D cultures supplied by RegeneMed (San Diego, CA) were treated with 30 µM RVX-208 over a time course (A) or the indicated concentrations of RVX-208 for 48 h (B). Data are the mean from independent triplicate samples, while error bars represent standard deviation. ^⁎p<0.05 versus DMSO treated samples at the same time point using two-tailed Student׳s t-tests.

Fig. 2

Comparison of effects of RVX-208 and JQ1 on ApoA-I protein secretion from cryopreserved primary human hepatocytes. Secreted total ApoA-I and proApoA-I protein levels were determined by ELISA in spent media from cells treated with 0.1% DMSO, 30 µM RVX-208 or 0.6 µM JQ1 for 72 h.