Identification of atrial fibrillation-associated microRNAs in left and right atria of rheumatic mitral valve disease patients

Abstract

MicroRNA (miRNA) is associated with the development and pathology of atrial fibrillation (AF). In this study, we performed miRNA profiling of left and right atrium samples from individuals with AF-associated rheumatic mitral valve disease (RMVD) to identify miRNAs that are differentially expressed between RMVD patients with AF and RMVD with sinus rhythm (SR) as controls, as well as between left and right atrium samples from RMVD with AF patients. We performed hematoxylin and eosin staining as well as scanning and transmission electron microscopy to examine in detail any morphological and physiological changes in cardiomyocytes from RMVD patients with AF or SR. Raman spectroscopy was performed to identify molecular and structural information of left and right atrium samples from RMVD with AF and SR. We also performed miRNA array profiling to separately profile miRNA expression patterns of right and left atrium samples from three independent RMVD patients with AF and in a mixed pool of 10 RMVD patients with SR. Morphological and physiological analysis showed distinct shapes and structures of cardiomyocytes from the left and right atria of RMVD patients with AF or SR. The intensity of Raman spectroscopy of atrial tissues from RMVD patients with AF and with SR was different. miRNA profiling showed differential miRNA expression between RMVD patients with AF or SR, and between the left and right atria of RMVD patients with AF. Importantly, miRNAs showed consistent expression changes among all three patients, suggesting that these miRNAs have potential as markers for AF pathology. Our results revealed potential biomarker miRNAs for atrial fibrillation pathology in patients with RMVD. Meanwhile, our data suggested that miR-10b and miR-138-2, which were both significantly increased in the left atrium, are responsible for morphological and physiological phenotype differences between the left and right atria.

Identification of atrial fibrillation‐associated lncRNAs in atria from patients with rheumatic mitral valve disease

“…To date, detailed mechanisms between RMVD and AF are still poorly understood. In previous studies, we revealed differentially expressed miRNAs in RMVD patients with AF, which provided preliminary insights into the mechanism of AF pathology in RMVD (Yang et al, ). However, lncRNAs have not been fully investigated in RMVD patients with AF.…”

MiR-324-3p Regulates Fibroblast Proliferation via Targeting TGF-β1 in Atrial Fibrillation

“…28) Additionally, the latest study revealed that miR-324-3p was down-regulated in patients with AF-associated rheumatic mitral valve disease. 25) These studies have demonstrated that miR-324-3p plays an essential role in heart-related diseases. Conversely, Macconi, et al showed that miR-324-3p contributed to the development of fibrosis in progressive nephropathy by targeting prolyl endopeptidase (Prep).…”

“…22) Additionally, evidences reported that miR-30, miR-133, and miR-590 were involved in AF development through the regulation of fibrosis. 23,24) Conversely, the previous study has revealed the decreased miR-324-3p expression in AF 25) . In the present study, through genome-wide miRNAs sequencing, we also found the decreased miR-324-3p expression in patients with AF.…”

“…A previous study has revealed the decreased miR-324-3p expression in AF. 25) To investigate the effect of miR-324-3 p on AF, the clinical AF samples and AF rat models were obtained to testify miR-324-3p expression. Consistently, in the rats of AF, the levels of miR-324-3p were showed to obviously reduce compared with those in the control rats ( Figure 2E).…”

Bioinformatics Analysis of Key Genes and Pathways for Obesity Associated Type 2 Diabetes Mellitus as a Therapeutic Target

“…To validate the accuracy of the target genes, miRNAs and TFs identified by target gene - miRNA regulatory network and target gene - TF regulatory network analysis. Yan et al [174], Wang et al [175], Yan et al [176] and Guo et al [177] showed that hsa-mir-4329, hsa-mir-3685, hsa-mir-6124, hsa-mir-1297 and SMARCA4 expression can be associated with cardiovascular diseases progression, but these genes might be essential for advancement of obesity associated type 2 diabetes mellitus. hsa-mir-1299 [178], hsa-mir-4779 [179] and hsa-mir-4459 [180] play a crucial role in type 2 diabetes mellitus.…”