Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:Obesity-induced secretory disorder of adipose tissue-derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in Angiotensin II (AngII)-infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue, as well as more severe cardiac remodeling compared to control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow specific uPA knockdown decreased active PDGF-DD level in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte, that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.
Project description:In order to study the capacity of the myocardium to recover from a stress causing several features of heart failure with preserved ejection fraction, C57Bl6/J male and female mice received or not for 28 days an angiotensin II (AngII; 1,5 mg/kg/day) continuous infusion in combination with a high fat diet (HFD). Half of the animals were then euthanized. The remaining ones had the AngII infusion stopped and their diet normalized. In addition, voluntary exercise was initiated by introducing a running wheel in the animals cage for an additional 28 days.
Project description:Physiological and pathological stimuli result in distinct anatomic forms of cardiac hypertrophy, but the head-to-head comparison of molecular regulation between physiological and pathological cardiac hypertrophy is less well understood, especially at the DNA methylation level. We conducted an in vitro study using human cardiomyocyte cell line AC16 exposed to angiotensin II (AngII) and insulin-like growth factor 1 (IGF-1) to mimic pathologically and physiologically hypertrophic heart models, respectively. Whole genome DNA methylation patterns were profiled by the Infinium human MethylationEPIC platform with >850K DNA methylation loci. We detected 194 loci that are significantly differentially methylated after AngII treatment (vs control) with 50.0% hypermethylated, and 206 significant loci after IGF-1 treatment (vs control) with 45.1% hypermethylated (Adjusted P < 0.05). Mapping the significant loci to genes, we identified 158 genes corresponding to AngII treatment and 175 genes to IGF-1 treatment, with 67 genes overlapping between AngII and IGF-1.
Project description:The genetic background of mice used in this study is mainly C57BL/6J with a small contribution from 129/Sv and DBA/2J strains. Male littermates were received continuous administration of AngII for 7 days at 0.9ug/hour. On day 7 of AngII infusion, the blood pressure of infused mice was (mmHg, mean ± SD) 156 ± 1, while the control littermates remained normotensive (106 ± 9). Keywords: other
Project description:AngII infusion in mouse is a classic model of cardiac hypertrophy. Here we aimed to understand how non-myocytes in the myocardium respond to AngII stimulation.
