A5085204923- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Lipoproteins and Cardiovascular Health
- Pancreatic function and diabetes
- Lysosomal Storage Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Diabetes Treatment and Management
- Caveolin-1 and cellular processes
- Atherosclerosis and Cardiovascular Diseases
- Renal Diseases and Glomerulopathies
- Drug Transport and Resistance Mechanisms
- Cancer, Lipids, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Neonatal Health and Biochemistry
- Sirtuins and Resveratrol in Medicine
- Diet and metabolism studies
- Mitochondrial Function and Pathology
- Cholesterol and Lipid Metabolism
- Career Development and Diversity
- Nuclear Receptors and Signaling
- Metabolism and Genetic Disorders
- Diabetes Management and Research
- Sphingolipid Metabolism and Signaling
- Retinopathy of Prematurity Studies
- Cardiovascular Function and Risk Factors
Pediatrics and Genetics
2023
University Medical Center Groningen
2018-2022
University of Groningen
2018-2022
University of Alberta
2020
Background: Although empagliflozin was shown to profoundly reduce cardiovascular events in diabetic patients and blunt the decline cardiac function nondiabetic mice with established heart failure (HF), mechanism of action remains unknown. Methods Results: We treated 2 rodent models HF 10 mg/kg per day measured activation NLRP3 (nucleotide-binding domain-like receptor protein 3) inflammasome heart. show for first time that beneficial effects reduced ejection fraction (HF [HFrEF]; n=30–34)...
Background: Previous studies have shown beneficial effects of acute infusion the primary ketone body, β-hydroxybutyrate, in heart failure (HF). However, whether chronic elevations circulating ketones are remains unknown. Methods: To chronically elevate mice, we deleted expression ketolytic, rate-limiting-enzyme, SCOT (succinyl-CoA:3-ketoacid-CoA transferase 1; encoded by Oxct1 ), skeletal muscle. Tamoxifen-inducible muscle-specific Muscle− / − knockout (n=32) mice and littermate controls...
The evolutionary conserved Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex is one of the crucial multiprotein complexes that facilitates endosomal recycling transmembrane proteins. Defects in WASH components have been associated with inherited developmental neurological disorders humans. Here, we show hepatic ablation component Washc1 chow-fed mice increases plasma concentrations cholesterol both LDLs HDLs, without affecting content, synthesis, biliary excretion, or bile...
The copper metabolism MURR1 domains/coiled-coil domain containing 22/coiled-coil 93 (CCC) complex is required for the transport of low-density lipoprotein receptor (LDLR) and LRP1 (LDLR-related protein 1) from endosomes to cell surface hepatocytes. Impaired functioning hepatocytic CCC causes hypercholesterolemia in mice, dogs, humans. Retriever, a consisting subunits VPS26C, VPS35L, VPS29, associated with CCC, but its role endosomal unclear. We here investigated contribution retriever...
Abstract Disturbed cholesterol homeostasis is associated with multiple diseases, such as atherosclerotic cardiovascular disease, lysosomal storage disorders, and neurodegenerative disorders. The endo-lysosomal network plays a central role in the distribution of between subcellular membranes, but processes controlling this transport are still not well-defined. Here, we investigate impact hepatic Retromer, an endosomal sorting complex consisting VPS35, VPS26, VPS29, on by using liver-specific...
We recently that the CCC and WASH complexes coordinate endosomal LDLR recycling.In vitro studies have implicated both are recruited to endosomes trough a binding with retromer subunit VPS35.Remarkably, recent study has shown can localize independently of VPS35.Furthermore, dominant-negative mutation in VPS35 is correlated Parkinson's disease and, our knowledge, not been associated dyslipidemia.These controversial results made us decide assess contribution LDL metabolism.