A5015290192- Apelin-related biomedical research
- Cardiovascular Health and Disease Prevention
- Lymphatic System and Diseases
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cardiac Health and Mental Health
- Diet and metabolism studies
- Histone Deacetylase Inhibitors Research
- GDF15 and Related Biomarkers
- Nutrition and Health in Aging
- Metabolomics and Mass Spectrometry Studies
- Stress Responses and Cortisol
- Adipokines, Inflammation, and Metabolic Diseases
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
Pfizer (United States)
2019-2023
Acceleron Pharma (United States)
2020
The lymphatic vasculature is involved in the pathogenesis of acute cardiac injuries, but little known about its role chronic dysfunction. Here, we demonstrate that angiotensin II infusion induced inflammation and fibrosis at 1 week caused dysfunction impaired transport 6 weeks mice, while co-administration VEGFCc156s improved these parameters. To identify novel mechanisms underlying this protection, RNA sequencing analysis distinct cell populations revealed specifically modulated II-induced...
Branched chain amino acid (BCAA) catabolic impairments have been implicated in several diseases. ketoacid dehydrogenase (BCKDH) controls the rate limiting step BCAA degradation, activity of which is inhibited by BCKDH kinase (BDK)-mediated phosphorylation. Screening efforts to discover BDK inhibitors led identification thiophene PF-07208254, improved cardiometabolic endpoints mice. Structure-activity relationship studies a thiazole series inhibitors; however, these did not improve metabolism...
Mouse models are used to model human diseases and perform pharmacological efficacy testing advance therapies humans; most of these studies conducted in room temperature conditions. At (22°C), mice cold-stressed must use brown adipose tissue (BAT) maintain body temperature. This cold stress increases catecholamine tone adipocyte lipid release via lipolysis, which will fuel adaptive thermogenesis. Maintaining rodents at thermoneutral temperatures (28°C) ameliorates the need for thermogenesis,...
Circulating increases in branched chain amino acid (BCAA) levels have long been associated with type II diabetes and metabolic syndrome. Emerging data also suggest that impaired BCAA catabolism may play a role heart failure progression. are catabolized via the ketoacid (BCKA) dehydrogenase enzyme complex (BCKDH). BCKD kinase (BCKDK) is negative regulator of through its inhibitory phosphorylation BCKDHE1a subunit, phosphatase PPM1k dephosphorylates this same site to activate catabolism. Using...
Previous studies have indicated that cardiac lymphatics are involved in the pathogenesis of acute injuries. However, role chronic heart failure remains unclear. The goal this study is to investigate development failure, and test hypothesis improving lymphatic vascular function will therapeutic benefits failure. First, we characterized endothelial marker expression human hearts from normal or patients, a trend towards reduced was observed. These data suggested vessels may be impaired To...
Abstract Platinum-based chemotherapy is associated with nausea/emesis, anorexia and weight loss which reduce patient quality of life limit treatment adherence potentially leading to poor outcomes. Cisplatin increases circulating growth differentiation factor 15 (GDF-15), a cytokine that induces conditioned taste aversion, in preclinical models. GDF-15 signals through the hindbrain receptor glial cell-derived neurotrophic alpha-like (GFRAL). Cisplatin-induced anorexia/weight was attenuated...