A5029246101- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Multiple Myeloma Research and Treatments
- Circadian rhythm and melatonin
- Ubiquitin and proteasome pathways
- Lysosomal Storage Disorders Research
- Peptidase Inhibition and Analysis
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Complement system in diseases
- Renal and Vascular Pathologies
- Diabetes Treatment and Management
- Heart Rate Variability and Autonomic Control
- Platelet Disorders and Treatments
- Eicosanoids and Hypertension Pharmacology
- Muscle and Compartmental Disorders
- Biomedical Research and Pathophysiology
- Autoimmune and Inflammatory Disorders Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Stroke Rehabilitation and Recovery
- Infrared Thermography in Medicine
- Sleep and Wakefulness Research
- Spaceflight effects on biology
- Neurogenesis and neuroplasticity mechanisms
- Photoreceptor and optogenetics research
Resverlogix (Canada)
2017-2023
University of California, Irvine
2022
VA Palo Alto Health Care System
2021
Amsterdam UMC Location University of Amsterdam
2020
University of Calgary
2009-2019
Apabetalone (RVX-208) is a bromodomain and extraterminal protein inhibitor (BETi) that in phase II trials reduced the relative risk (RR) of major adverse cardiac events (MACE) patients with cardiovascular disease (CVD) by 44% diabetic CVD 57% on top statins. A III trial, BETonMACE, currently assessing apabetalone's ability to reduce MACE statin-treated post-acute coronary syndrome type 2 low high-density lipoprotein C. The leading cause atherosclerosis, driven dysfunctional lipid metabolism...
Abstract Background Patients with cardiovascular disease (CVD) and type 2 diabetes (DM2) have a high residual risk for experiencing major adverse cardiac event. Dysregulation of epigenetic mechanisms gene transcription in innate immune cells contributes to CVD development but is currently not targeted by therapies. Apabetalone (RVX-208) small molecule inhibitor bromodomain extra-terminal (BET) proteins—histone acetylation readers that drive pro-inflammatory pro-atherosclerotic transcription....
The subgranular zone of the hippocampal formation gives rise to new neurons that populate dentate gyrus throughout life. Cells in hippocampus exhibit rhythmic clock gene expression and circadian is known regulate cycle cell division other areas body. These facts suggest may adult neurogenesis as well. In present study, was examined arrhythmic Bmal1 knockout (-KO) mice their heterozygous wildtype littermates. Proliferation survival newly generated cells were using bromodeoxyuridine labelling,...
Epigenetic mechanisms are implicated in transcriptional programs driving chronic kidney disease (CKD). Apabetalone is an orally available inhibitor of bromodomain and extraterminal (BET) proteins, which epigenetic readers that modulate gene expression. In the phase 3 BETonMACE trial, apabetalone reduced risk major adverse cardiac events (MACE) by 50% CKD subpopulation, indicating favorable effects along kidney-heart axis. Activation human renal mesangial cells (HRMCs) to a contractile...
Abstract Fabry disease (FD) is a rare X‐linked disorder of lipid metabolism, characterized by the accumulation globotriaosylceramide (Gb3) due to defective lysosomal enzyme, α‐galactosidase. Gb3 deposits activate immune‐mediated systemic inflammation, ultimately leading life‐threatening consequences in multiple organs such as heart and kidneys. Enzyme replacement therapy (ERT), standard care, less effective with advanced tissue injury inflammation patients FD. Here, we showed that MCP‐1...
Chronic systemic inflammation contributes to cardiovascular disease (CVD) and correlates with the abundance of acute phase response (APR) proteins in liver plasma. Bromodomain extraterminal (BET) are epigenetic readers that regulate inflammatory gene transcription. We show BET inhibition by small molecule apabetalone reduces APR protein expression human hepatocytes, mouse models, plasma from CVD patients. Steady-state serum amyloid P, plasminogen activator inhibitor 1, ceruloplasmin, linked...
Abstract Brain vascular inflammation is characterized by endothelial activation and immune cell recruitment to the blood vessel wall, potentially causing a breach in – brain barrier, parenchyma inflammation, decline of cognitive function. The clinical-stage small molecule, apabetalone, reduces circulating markers improves scores elderly patients targeting epigenetic regulators gene transcription, bromodomain extraterminal proteins. However, effect apabetalone on cytokine-activated cells...
Abstract Apabetalone (RVX-208) is an orally available small molecule bromodomain & extraterminal (BET) protein inhibitor that targets the second (BD2) of BET proteins. returns dysregulated BET-dependent transcription toward normal physiological levels. In phase 2 trials, apabetalone treatment reduced incidence major adverse cardiac events by 44% in CVD patients and 57% diabetic patients. Previous studies have highlighted apabetalone's positive impact on vascular calcification (VC)...
Introduction: Apabetalone is an orally available small molecule that affects gene transcription by inhibiting BET protein interactions with acetylated histones and factors. in late stage clinical development for the treatment of cardiovascular disease (CVD). Clinical trials show apabetalone well tolerated has a favorable safety profile. Recent evidence indicates this drug could be repurposed to treat COVID-19 reducing expression angiotensin converting enzyme 2 (ACE2) receptor essential...
Abstract Background and Aims Major adverse cardiac events (MACE) are a leading cause of mortality in patients with chronic kidney disease (CKD). Apabetalone is an orally available inhibitor bromodomain & extraterminal (BET) proteins – epigenetic readers that modulate gene expression involved fibrosis inflammation. In the phase 3 BETonMACE trial CVD diabetes mellitus (NCT02586155), apabetalone reduced MACE by 50% subpopulation CKD (eGFR < 60 mL/min/1.73 m2; HR 0.50 95% CI 0.26,0.96...
Facioscapulohumeral dystrophy (FSHD) is a muscle disease caused by inappropriate expression of the double homeobox 4 (DUX4) gene in skeletal muscle, and its downstream activation pro-apoptotic transcriptional programs. Inhibitors DUX4 have potential to treat FSHD. Apabetalone clinical-stage bromodomain extra-terminal (BET) inhibitor, selective for second on BET proteins. Using primary human cells from FSHD type 1 patients, we evaluated apabetalone ability counter DUX4′s deleterious effects...
INTRODUCTION AND AIMS:We previously showed that the transcription factor MafB is essential for differentiation and foot process formation of podocytes.However, role in maintenance podocytes was not established, because conventional deficient mice die during perinatal period.The function MAFB human kidney disease also established. METHODS:In order to address this question, we generated inducible podocytespecific knockout using tamoxifen-inducible Cre-loxP system.We recently obtained flox/...
Methods:We consecutively included patients submitted to a second coronary angiography more than 3 months after first angiography, independently of the clinical reason for procedure.We calculated lesion severity score each patient compare non-revascularized lesions according diameter stenosis: 1 point stenosis 50-70%, 2 points 70-99%, if 100% occlusion.The same was applied in angiography.The difference between scores defined as primary endpoint.Results: A total 439 were included, which 211...