Project description:The right and left atria have different susceptibilities towards developing arrhythmias, with left atrial arrhythmias more commonly observed. To study potential underlying causes of this difference between the two upper chambers of the heart, four human left-right atrial pairs were subjected to whole-genome expression analyses via next generation sequencing of small RNAs, including microRNAs (miRNAs), and polyA enriched mRNAs. Using a paired sample design, significant differences in gene expression were found between the left and right atria in both the poly-A and small RNA fractions. Hsa-miR-143 was the most highly expressed miRNA in the atria as quantified by RNA-seq. Gene expression differences established during development are retained into adulthood including that of PITX2 and BMP10. In addition ten novel non-coding RNAs were found to be differentially expressed between the left and right atrias .
Project description:Next Generation RNA Sequencing was carried out on human paired left and right atrial appendages from patients with and without Atrial Fibrillation. EdgeR software was used to show a total of 247 genes were found to have significant differential expression between left and right atria.
Project description:Background: Chronic atrial fibrillation (AF) is a complication associated with the dilated atria of patients with valvular heart disease and contributes to worsened pathology. Methods and Results: Using microarray technology, we examined microRNA (miR) expression profiles in right and left atrial appendage tissue from valvular heart disease (VHD) patients. Right atrial appendage from patients undergoing coronary artery bypass grafting (CABG) and left atrial (LA) appendage from healthy hearts not used for transplant were used as controls. VHD induced different changes in miR expression in LA compared with right atria (RA). Fifty-two (52) miRs were altered by VHD in LA, compared with 5 in RA tissue. There was no detectable effect of chronic AF on miR expression in LA tissue, but miR expression in RA was strongly influenced by AF, with 47 miRs showing differential expression. LA volume correlated with miR expression changes in both LA and RA, but the affected miRs were different for the two atrial groups. Conclusions: VHD and AF influence miR expression patterns in LA and RA, but these are affected differently by disease progression and by the development of AF. These findings provide new insights into the progression of VHD. RA tissue is not a useful surrogate for LA in studies of mitral valve disease. 34 arrays from either the left or right atrium from patients with Valvular Heart Disease (VHD), patients undergoing coronary artery bypass grafting (CABG), or healthy controls. Arrays in this series were generated on V2 and V3 Agilent microRNA arrays and analysed in combination.
Project description:To identify pathway and mechanism undergoing post operative atrial fibrillation, we check transcriptomic expression of patients with and without post operative atrial fibrillation development and compare up and down regulated genes and their pathways. Right atrial appendage were obtained from patients undergoing cardiac surgery.
Project description:Background: Chronic atrial fibrillation (AF) is a complication associated with the dilated atria of patients with valvular heart disease and contributes to worsened pathology. Methods and Results: Using microarray technology, we examined microRNA (miR) expression profiles in right and left atrial appendage tissue from valvular heart disease (VHD) patients. Right atrial appendage from patients undergoing coronary artery bypass grafting (CABG) and left atrial (LA) appendage from healthy hearts not used for transplant were used as controls. VHD induced different changes in miR expression in LA compared with right atria (RA). Fifty-two (52) miRs were altered by VHD in LA, compared with 5 in RA tissue. There was no detectable effect of chronic AF on miR expression in LA tissue, but miR expression in RA was strongly influenced by AF, with 47 miRs showing differential expression. LA volume correlated with miR expression changes in both LA and RA, but the affected miRs were different for the two atrial groups. Conclusions: VHD and AF influence miR expression patterns in LA and RA, but these are affected differently by disease progression and by the development of AF. These findings provide new insights into the progression of VHD. RA tissue is not a useful surrogate for LA in studies of mitral valve disease.
Project description:Background: Atrial fibrillation (AF) causes atrial remodeling, and the left atrium (LA) is the favored substrate for maintaining AF. However, it remains unclear if AF remodels both atria differently and contributes to LA arrhythmogenesis and thrombogenesis. Results: AF was associated with differential LA-to-RA gene expression related to specific ion channels and pathways as well as upregulation of thrombogenesis-related genes in the LA appendage. Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF. Paired left atrial and right atrial specimens were obtained from 13 patients with persistent AF receiving valvular surgery. The Paired specimens were sent for microarray comparison. Selected results were validated by quantitative real time-PCR (q-PCR) and Western blotting. Ultrastructural changes in the atria were evaluated by immunohistochemistry.
