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:The objective of the present study is to explore the role of human MSC derived adipocytes transduced with/without lenti adipo-NaKtide or lenti adipo-scrambled NaKtide in experimental uremic cardiomyopathy. We investigated the pathophysiological changes in recipient mice that underwent partial nephrectomy surgery, as a model of uremic cardiomyopathy, and implanted with NaKtide transfected human MSC derived adipocytes. We aimed to demonstrate that adipocyte specific NaKtide reprograms the adipocyte phenotype and transplantation of these metabolically healthy adipocytes in diseased condition exhibits improved systemic and cardiovascular function, through intra-organ crosstalk.
Project description:Uremic pruritus (UP) is one of the common symptoms in patients with uremia, and its etiology and mechanism have not been fully understood. In view of the high incidence of UP, finding the specific changed proteins in blood of UP patients will help revealing the potential biological mechanisms of UP and explore biomarkers. In this study, LC-MS/MS based data independent acquisition (DIA) mode was used to analyze the serum samples of 54 UP patients (DKD-UP, HN-UP and GN-UP, n=18 for each), 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD).
Project description:MicroRNAs negatively regulate gene expression and may serve as biomarkers for human cardiomyopathy. In the domestic cat, hypertrophic cardiomyopathy (HCM) represents the most common primary cardiomyopathy. In humans, the etiology of HCM is linked to mutations in genes of contractile muscle proteins, while in cats a clear proof for causal mutations is missing. The etiology of feline HCM is uncertain. Diagnosis is made by heart ultrasound examination and measuring the serum level of N-terminal pro B-type natriuretic peptide. The purpose of this study was to investigate whether microRNA profiles in the serum of cats with HCM are different from the profiles of healthy cats and whether specific miRNAs can be detected to serve as potential biomarkers for feline HCM or may help in understanding the etiology of this disease Blood was drawn from two groups of cats: 12 healthy cats and 11 cats suffering from hypertrophic cardiomyopathy. After clotting, samples were centrifuged and total mRNA was extracted from serum. These 23 serum samples were analyzed and the groups were compared
Project description:MicroRNAs negatively regulate gene expression and may serve as biomarkers for human cardiomyopathy. In the domestic cat, hypertrophic cardiomyopathy (HCM) represents the most common primary cardiomyopathy. In humans, the etiology of HCM is linked to mutations in genes of contractile muscle proteins, while in cats a clear proof for causal mutations is missing. The etiology of feline HCM is uncertain. Diagnosis is made by heart ultrasound examination and measuring the serum level of N-terminal pro B-type natriuretic peptide. The purpose of this study was to investigate whether microRNA profiles in the serum of cats with HCM are different from the profiles of healthy cats and whether specific miRNAs can be detected to serve as potential biomarkers for feline HCM or may help in understanding the etiology of this disease
Project description:Transcriptome analysis of human coronary arterial endothelial cells (HCAEC) primary cultures exposed to uremic serum from patients with stage 4-5 cardiovascular diseases (CKD) without myocardial infarction (USI) and stage 4-5 CKD with myocardial infarction (UCI). Gene expression profile of human coronary arterial endothelial cells (HCAEC) primary cultures exposed to uremic serum from of patients with chronic kidney disease (CKD) that explore which pathways are involved in in the development of cardiovascular disease. The metabolic pathway significantly represented was the MAPK signaling pathway, suggesting that the effects of uremic toxins present in patients with CDK, on the primary cultures of HCAEC provides a more informative model for the study of molecular mechanisms that lead to the development of endothelial dysfunction secondary to CKD.
Project description:We hope to determine the importance of different genes (including B receptors) in anthracycline-induced cardiomyopathy. This has important benefits to patients exposed to anthracyclines, as this could help determine whether certain individuals have increased susceptibility to cardiac injury.
Project description:In this study RNA-Seq was performed in anthracycline- exposed childhood cancer survivors who had cardiomyopathy (cases) matched to those without cardiomyopathy (controls) to understand the pathogenesis of anthrcaycline-related cardiomyopathy