Project description:To identify the circRNA expression profiles in HF patients’ plasma and to evaluate the potential application of circRNAs for HF diagnosis, circRNA microarrays were performed on plasma samples obtained from HF patients and healthy controls. The RNAs of the plasma from the HF and control groups were extracted for microarray analysis. The purified RNAs were hybridized to a microarray (Agilent human circRNA Array V2.0) containing 170,340 human circRNA probes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results.
Project description:Heart failure is associated with degradation of cell functions and extracellular matrix proteins, but the trigger mechanisms are uncertain. Our recent evidence in acute multiorgan failure suggests that active digestive enzymes leak out of the small intestine into the systemic circulation and cause cell dysfunctions and organ failure. Accordingly, we investigated in morning fasting plasma of heart failure (HF) patients the presence of pancreatic trypsin, a major enzyme responsible for digestion. Western analysis shows that trypsin in plasma is significantly elevated in HF compared to matched controls and their concentrations correlate with inflammatory biomarkers. The plasma trypsin levels in HF are accompanied by elevated pancreatic lipase concentrations. The trypsin has a significantly elevated activity as determined by substrate cleavage. Mass spectrometry shows that the number of proteins in the HF group is similar to controls while the number of peptides was increased about 20% in the HF patients. The peptides are derived from extracellular and intracellular protein sources and exhibit cleavage sites by trypsin as well as other degrading proteases. These results provide first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF.
Project description:RELEVANCE: Identifying early plasma protein biomarkers that predict the development of heart failure (HF) following myocardial infarction (MI) will help to stratify at risk subjects and provide insight into more effective therapeutic strategies. OBJECTIVE/HYPOTHESIS: The goal of this study was to determine markers of HF in African Americans, using plasma samples collected before the development of symptoms. We propose that early plasma glycoprotein changes will link to later development of heart failure. ApolipoproteinF will be the strongest indicator. METHODS: Plasma samples from a subset of Jackson Heart Study participants with a history of MI but without prevalent heart failure (HF) at visit 2 (2005-2008) were analyzed by glycoproteomics. Individuals were grouped into those who experienced subsequent HF hospitalization after visit 2 (n=15; 3 men/ 12 women) and those without HF hospitalization through 2012 (n=45; 24 men/ 21 women). N-linked plasma glycopeptides were quantified by solid-phase extraction coupled to mass spectrometry and identified using RefSeq and SwissProt. Proteins were mapped for biological processes and functional pathways using Ingenuity Pathway Analysis (IPA) and linked to clinical characteristics.
Project description:To establish changes in cardiac transcription profiles brought about by heart failure we collected myocardial samples from patients undergoing cardiac transplantation whose failure arises from different etiologies (e.g. idiopathic dilated cardiomyopathy, ischemic cardiomyopathy, alcoholic cardiomyopathy, valvular cardiomyopathy, and hypertrophic cardiomyopathy) and from "normal" organ donors whose hearts cannot be used for transplants. The transcriptional profile of the mRNA in these samples will be measured with gene array technology. Changes in transcriptional profiles can be correlated with the physiologic profile of heart-failure hearts acquired at the time of transplantation. Keywords: other
Project description:Heart failure (HF) is a deadly disease that is difficult to accurately diagnose. Circular RNAs (circRNAs) are a novel class of noncoding RNAs that might play important roles in many cardiovascular diseases. However, their role in HF remains unclear. CircRNA microarrays were performed on plasma samples obtained from three patients with HF and three healthy controls. The profiling results were validated by quantitative reverse transcription polymerase chain reaction. The diagnostic value of circRNAs for HF was evaluated by receiver operating characteristic (ROC) curves. The expression profiles indicated that 477 circRNAs were upregulated and 219 were downregulated in the plasma of patients with HF compared with healthy controls. Among the dysregulated circRNAs, hsa_circ_0112085 (p = 0.0032), hsa_circ_0062960 (p = 0.0006), hsa_circ_0053919 (p = 0.0074) and hsa_circ_0014010 (p = 0.025) showed significantly higher expression in patients with HF compared with healthy controls. The area under the ROC curve for hsa_circ_0062960 for HF diagnosis was 0.838 (p < 0.0001). Correlation analysis showed that the expression of hsa_circ_0062960 was highly correlated with B-type natriuretic peptide (BNP) serum levels. Some differential circRNAs were found to be related to platelet activity by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The landscape of circRNA expression profiles may play a role in HF pathogenesis and improve our understanding of platelet function in HF. Moreover, hsa_circ_0062960 has potential as a novel diagnostic biomarker for HF.