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Right atrial mechanism contributes to atrial fibrillation in a canine model of pulmonary arterial hypertension
Yang LIU, Xi-Yao ZHU, Zi-Liang SONG, Mu QIN, Chang-Hao XU, Xu LIU
, Available online  , doi: 10.11909/j.issn.1671-5411.2022.12.011
 OBJECTIVES To investigate proarrhythmic substrates of atrial fibrillation (AF) in a canine model of dehydromonophylline (DMCT)-induced pulmonary arterial hypertension (PAH). METHODS All cannines (n = 12) underwent baseline echocardiographic and hemodynamic examinations, 7 of which were injected with DMCT (3.0 mg/kg) to induce PAH via jugular vein cannulation. The control beagles (n = 5) were given the same dose of normal saline. Then, both groups were monitored by insertable cardiac monitors. Hemodynamic, echocardiographic, electrophysiological and histological examinations were performed 8 weeks later. RESULTS In PAH group, two died after the injection (mortality 28.6%). Thus, 10 beagles (PAH group: 5, control group: 5) underwent all the examinations. The pulmonary artery pressure increased significantly while the right atrium (RA) and right ventricle expanded slightly. Spontaneous AF episodes were recorded in all PAH canines 1 week after the injection. The AF burden increased rapidly from 1 week (7.6% ± 1.8%) and remained high after 2-3 weeks (32.0% ± 4.9% at 8 weeks). Compared with the control group, the PAH group had abbreviated effective refractory periods (ERPs), increased atrial ERP dispersion, and slower conduction velocities. Notably, AF susceptibility and atrial remodeling in RA was more significant those in LA, such as increased WOV (39.0 ± 6.5 vs. 28.0 ± 5.7 ms, P = 0.022), enlarged low voltage regions (7.66% ± 0.46% vs. 4.40% ± 0.55%, P < 0.0001) and fibrosis (8.22% ± 0.61% vs. 4.93% ± 0.60%, P < 0.0001). CONCLUSIONS  DMCT-induced canine PAH model increased the incidence of spontaneous and induced AF. The electrophysiological and structural remodeling of the RA facilitated the AF genesis.
A circRNA-miRNA-mRNA network identifcation for exploring underlying pathogenesis of human heart failure
Ran XU, Jian WU, Chun-Jie YANG, Le KANG, Yu-Yao JI, Chang LI, Zhi-Wen DING, Yun-Zeng ZOU
, Available online  , doi: 10.11909/j.issn.1671-5411.2022.10.016
 BACKGROUND  The molecular mechanisms of heart failure (HF) remain poorly understood. Studies have increasingly found circular RNA (circRNA) exists in heart. The aim of this study is to acquire potential functions of circRNAs in HF.  METHODS & RESULTS  We integrated RNA sequencing data to identify the characteristics of circRNAs expressed in heart and found that most circRNAs screened were < 2000 nt (89%); moreover, Chromosome 1 and Y contained the largest and least number of circRNAs (10.59% and 0.2%), respectively. Subsequently, a total of 238 differentially expressed circRNAs (DECs) were found and 203 host genes were discovered after excluding duplicate host genes and intergenic circRNAs. However, only 4 of 203 host genes of DECs were checked in differentially expressed genes (DEGs) of HF. Another, Gene Oncology (GO) analysis of DECs host genes was performed to elucidate the underlying pathogenesis of HF, suggesting that binding and catalytic activity accounted for a great part of DECs. The pathways related to immune system, metabolism and signal transduction were significantly enriched. Additionally, 1052 potentially regulated miRNAs from the top 40 DECs were collected to construct a circRNA–miRNA network and found that 470 miRNAs can be regulated by multiple circRNA, while others were regulated by a single circRNA. And further comparison with the top 10 mRNAs and their targeted miRNAs in HF showed DDX3Y and UTY were regulated by the most and least circRNA, respectively. Finally, four selected randomly DECs were validated by qRT-PCR.  CONCLUSION  These data showed that circRNAs have species and tissue specific expression features; although circRNAs expression independent on host genes, same types of genes between DECs and DEGs worked in HF. CircRNAs could regulate miRNAs as molecular sponges. Our data would enhance understanding of the important roles of circRNAs and lay a foundation for future investigations of HF molecular functions.