Journal
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
Volume 10, Issue 4, Pages 337-347Publisher
SPRINGER
DOI: 10.1007/s12265-017-9755-z
Keywords
Epigenetics; Bromodomain; Bromodomain and extraterminal protein; Biomarker; Inflammation; Complement cascade; Innate immunity; Cardiovascular disease; major acute cardiac event
Funding
- Resverlogix Corp.
Ask authors/readers for more resources
Apabetalone (RVX-208) is an epigenetic regulator developed to treat cardiovascular disease (CVD) that targets BET proteins. Through transcriptional regulation RVX-208 modulates pathways that underlie CVD including reverse cholesterol transport, vascular inflammation, coagulation, and complement. Using transcriptomics and proteomics we show that complement is one of the top pathways downregulated by RVX-208 in primary human hepatocytes (PHH) and in plasma from CVD patients. RVX-208 reduces basal and cytokine-driven expression of complement factors in PHH and in chimeric mice with humanized livers. Plasma proteomics of CVD patients shows that RVX-208 decreases complement proteins and regulators, including complement activators SAP and CRP. Circulating activated fragments C5a, C3b, and C5b-C6 are reduced by 51, 32, and 10%, respectively, indicating decreased activity of complement in patients. As complement components are linked to CVD and metabolic syndrome, including major acute cardiac events, modulating their levels and activity by RVX-208 may alleviate risks associated with these diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available