RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease.
Atherosclerosis
; 247: 48-57, 2016 04.
Article
em En
| MEDLINE
| ID: mdl-26868508
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Doenças Cardiovasculares
/
Apolipoproteína A-I
/
Hepatócitos
/
Aterosclerose
/
HDL-Colesterol
/
Fígado
/
Hipolipemiantes
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Atherosclerosis
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá