Project description:High incidence of heart failure (HF) is a typical characteristic of chronic kidney disease (CKD). However, the pathogenesis of CKD-associated HF remains elusive. Here, we investigated the changes in myocardial energy metabolism in CKD mice and explored the underlying mechanisms. To examine genome wide transcriptional changes in the heart of CKD mice, we performed microarray analysis using the Affymetrix Clariom S mouse.
Project description:Uremic cardiomyopathy is a clinically highly relevant cause of cardiovascular events in patients with chronic kidney disease (CKD). Additionally, after acute myocardial infarction (MI), CKD-patients exhibit an increased risk of death. To investigate the underlying molecular mechanisms causing the adverse effects of CKD on cardicac outcome after MI, male mice were fed with an adenine-supplemented diet combined with western type diet (CKD mice) or with western type diet only (control mice). Invasive heart function evaluation and histological analyses were performed 7 days after MI-induction through left anterior descending artery (LAD) ligation. For a deeper look on molecular level, RNA sequencing of heart tissue was performed.
Project description:To examine genome wide transcriptional changes in the heart of 5/6 nephrectomy CKD mice, we performed microarray analysis using the Affymetrix Clariom S array.
Project description:Cardiovascular disease is highly prevalent in patients with chronic kidney disease (CKD) and responsible for approximately half of CKD-related deaths. The mechanisms underlying the detrimental impact of CKD on the heart are still incompletely understood, but CKD is associated with endocrinal, inflammatory and hemodynamic changes that impact the heart and may contribute to the development of uremic cardiomyopathy.
Project description:Accumulation of oxalate in patients with chronic kidney disease (CKD) is associated with CKD progression and an increased risk of cardiac death. Whether reducing oxalate slows CKD progression and prevents cardiovascular complications remains unexplored. We colonized Oxalobacter formigenes (Oxf), an oxalate-degrading microbiome, in the intestines of control and CKD mice fed with 1% hydroxyproline for 23 weeks. RNA-seq analysis of heart tissues of CKD mice reveals dysregulated expression of metabolic pathways and Oxf colonization reverses these changes. These findings demonstrate that oxalate accumulation plays a role not only in CKD progression but also in cardiovascular complications.
Project description:The endogenous peptide Apelin is crucial for maintaining heart function in pressure overload and aging Experiment Overall Design: Heart samples from Apelin knockout mice with pressure overload and sham control together with the wild-type mice with pressure overload and sham were compared
Project description:Purpose: To define differentially regulated pathways in heart tissue from mice with chornic kidney disease (CKD) compared to age-matched controls. Methods: CKD was induced in 5-week-old, male 129X1/SvJ mice (JAX) through five-sixths nephrectomy in a two-step surgery (n=5). Age-matched mice undergoing bilateral sham surgeries served as controls (n=5). Heart tissue was collected at 8 weeks of CKD for next generation sequencing. Results: Hearts from mice with uremic cardiomyopathy yielded over 1,000 differentially-expressed mRNA transcripts compared to hearts from age-matched, sham-operated mice. Ingenuity biofunctions analysis identified significant enrichment for genes involved in Tissue Morphology, Immune Cell Trafficking, Cardiovascular Development and Function, and Humoral Immune Response. We focused on Ingenuity canonical pathways involving inflammation and immune system function including pathways needed for a T-cell mediated response: leukocyte extravasation, antigen presentation, dendritic cell maturation, T cell co-stimulatory signaling, and T-helper cell differentiation. Conclusions: Left ventricles from mice with CKD display differential expression in a number of pathways suggesting inflammation and surprisingly involved genes involved in the adaptive immune system.
Project description:After induction of ischemic chronic heart failure (CHF), mice exhibited depression-like behavior, in terms of increased anhedonia, and decreased both exploratory activity and interest in novelty. On histology, ischemic CHF mice showed no alterations in overall cerebral morphology. To further evaluate relevant behavioral changes found in CHF mice, RNA-sequencing analysis of prefrontal cortex and hippocampus - the brain regions, whose structural and functional alterations are associated with an increased risk for developing major depressive disorder - and of left myocardial tissue was performed in CHF vs. sham-operated animals. RNA-sequencing revealed relevant changes in hippocampal or prefrontal cortical expression of genes responsible for axonal vesicle transport (Kif5b), signal transduction (Arc, Gabrb2), limitation of inflammation (RORA; Nr4a1) and of hypoxic brain damage (Hif3a). Besides, the actual literature describes some of the genes (RORA, Gabrb2, Npas4, and Junb) being associated with depression-like behavior. Nr4a1 significantly regulated in both brain and heart tissue after induction of ischemic CHF could be a potential link and reveals the central role of inflammation in the interrelation of the brain and the failing heart. Heart failure vs. sham-operation were performed in C57BL/6 male mice. After development of chronic heart failure (CHF) 8 weeks after the operation RNA was extracted out of prefrontal cortex, hippocampus and left ventricular myocardium in both groups. RNA of 3 ischemic CHF mice versus 6 sham operated mice was pooled and further subjected to RNA sequencing. To fabricate singular pools each probe of the group equally contributed with the final amount of 2 µg RNA per pool with the result that we had 6 different pools to be further evaluated. The mRNA profile was generated by IGA Technology, Italy (http://www.igatechnology.com/) by deep sequencing, using Illumina HiSeq 2000 platform (HiSeq). CLC-Bio Genomics Workbench software (CLC Bio, Denmark) was used to calculate gene expression levels based on Mortazavi et al. (Nat Methods. 2008;5:621-628) approach.
Project description:This project involves TMT-labeled proteomics analysis of mitochondria isolated from skeletal muscle, heart, and kidney of mice with and without chronic kidney disease (CKD). CKD was induced by adenine-supplementation of the diet for 6 months. Mouse strain was C57BL6J mice from Jackson Lab, aged 6 months prior to start of the diet. Mitochondria were isolated from skeletal muscle, heart, and kidney and immediately snap frozen and stored at -80C until processing.