Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels mediate pacemaker currents in the atrium. The microRNA (miR) families miR-1 and miR-133 regulate the expression of multiple genes involved in myocardial function, including HCN channels. It was hypothesized that age-dependent changes in HCN2, HCN4, miR-1 and miR-133 expression may contribute to age-associated atrial fibrillation, and therefore the correlation between expression levels, among adult (≤65 years) and aged patients (≥65 years), and sinus rhythm was determined. Right atrial appendage samples were collected from 60 patients undergoing coronary artery bypass grafting. Reverse transcription-quantitative polymerase chain reaction (PCR) and western blot analyses were performed in order to determine target RNA and protein expression levels. Compared with aged patients with sinus rhythm, aged patients with atrial fibrillation exhibited significantly higher HCN2 and HCN4 channel mRNA and protein expression levels (P<0.05), but significantly lower expression levels of miR-1 and miR-133 (P<0.05). In addition, aged patients with sinus rhythm exhibited significantly higher expression levels of HCN2 and HCN4 channel mRNA and protein (P<0.05), but significantly lower expression levels of miR-1 and -133 (P<0.05), compared with those of adult patients with sinus rhythm. Expression levels of HCN2 and HCN4 increased with age, and a greater increase was identified in patients with age-associated atrial fibrillation compared with that in those with aged sinus rhythm. These electrophysiological changes may contribute to the induction of ectopic premature beats that trigger atrial fibrillation.

MicroRNAs (miRNAs) are a class of non-coding small RNAs that play important roles in the regulation of gene expression. Although animal miRNAs have been extensively studied in model systems, less is known in other animal with limited genome sequence data, including Chinese giant salamander (Andrias davidianus). The identification of the full repertoire of miRNAs expressed in the liver, spleen and muscle of A. davidianus would significantly increase our understanding for physiological function of A. davidianus, in this ancient and endangered urodele amphibian. In this study, three independent small RNA libraries were constructed from the liver, spleen and muscle of A. davidianus. The libraries were subjected to high-throughput sequencing by using the Illumina deep sequencing. As a result, a total of 12,831,239, 13,592,195 and 9,887,531 raw reads representing 2,240,771, 1,363,266 and 1,964,252 clean reads per library were obtained separately. Through bioinformatics analysis, we identified total of 553 known miRNAs and 44 putative novel miRNAs in our small RNA dataset from liver, spleen and muscle tissues. Five known miRNAs (gga-miR-10a-5p, pma-miR-29d-5p, aca-miR-338-3p, hsa-miR-455-3p and ssa-miR-2184-5p_R-1) and three novel miRNAs (PC-5p-891_1763, PC-5p-32538_50 and PC-3p-33645_48) showed different expression in eight different tissues as revealed by stem-loop qPCR analysis. This study characterized the miRNA of A. davidianus for the first time, which provides an opportunity for further understanding of miRNA regulation function in A. davidianus ranked as living fossils.

Our findings demonstrate that genetic defects in AGTR2 and apelin genes by themselves may play an independent leading role in determining susceptibility to hypertension in both genders.

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