Objective: To investigate the expression profile of circular RNAs (circRNAs) and proposed circRNA–microRNA (miRNA) regulatory network in atrial fibrillation (AF). Methods: Atrial tissues from patients with persistent AF with rheumatic heart disease and non-AF myocardium with normal hearts were collected for circRNA differential expression analyses by high-throughput sequencing. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the differentially expressed genes and AF-related pathways. Co-expression networks of circRNA–miRNA were constructed based on the correlation analyses between the differentially expressed RNAs. Quantitative reverse transcription polymerase chain reaction (PCR) was performed to validate the results. Results: A total of 108 circRNAs were found to be differentially expressed in AF. Among them, 51 were up-regulated, and 57 were down-regulated. Dysregulated circRNAs were validated by quantitative real-time PCR. The GO and KEGG pathway enrichment analyses were executed to determine the principal functions of the significantly deregulated genes. Furthermore, we constructed correlated expression networks between circRNAs and miRNAs. circRNA19591, circRNA19596, and circRNA16175 interacted with 36, 28, and 18 miRNAs, respectively; miR-29b-1-5p and miR-29b-2-5p were related to 12 down-regulated circRNAs, respectively. Conclusion: Our findings provide a novel perspective on circRNAs involved in AF due to rheumatic heart disease and establish the foundation for future research of the potential roles of circRNAs in AF.

Vascular endothelial growth factor (VEGF), an independent mitogen, has been reported to induce angiogenesis and thus attenuates the damage induced by myocardial infarction (MI). VEGF165 is the most abundant and predominant isoform of VEGF. This study investigates whether this effect could be strengthened by local intramyocardial injection of VEGF165 along with a novel biodegradable Dex-PCL-HEMA/PNIPAAm hydrogel and ascertains its possible mechanism of action. Rat models of myocardial infarction were induced by coronary artery ligation. Phosphate-buffered saline (PBS group), Dex-PCL-HEMA/PNIPAAm hydrogel (Gel group), phosphate-buffered saline containing VEGF165 (VP group), and hydrogel containing VEGF165 (VPG group) were injected into a peri-infarcted area of cardiac tissue immediately after myocardial infarction, respectively. The sham group was thoracic but without myocardial infarction. The injection of VEGF165 along with a hydrogel induced angiogenesis, reduced collagen content and MI area, inhibited cell apoptosis, increased the level of VEGF165 protein and the expression of flk-1 and flt-1, and improved cardiac function compared with the injection of either alone after MI in rats. The results suggest that injection of VEGF165 along with a hydrogel acquires more cardioprotective effects than either alone in rat with MI by sustained release of VEGF165, then may enhance the feedback between VEGF and its receptors flk-1 and flt-1.

Basic fibroblast growth factor (bFGF), a known angiogenic factor, may provide a potential strategy for the treatment of myocardial infarction (MI), but it is limited by a relatively short half-life. Dex-PCL-HEMA/PNIPAAm hydrogel provides a reservoir for the controlled release of growth factors. The aim of the current study was to evaluate the effects of bFGF incorporated into a Dex-PCL-HEMA/PNIPAAm hydrogel on angiogenesis and cardiac health in a rat model of acute MI, induced by coronary artery ligation. Phosphate-buffered solution (PBS group), Dex-PCL-HEMA/PNIPAAm hydrogel (Gel group), bFGF in phosphate-buffered solution (bFGF group) or bFGF in hydrogel (Gel + bFGF group) was injected into a peri-infarcted area of cardiac tissue immediately following MI. On day 30 post-surgery, cardiac function was assessed by echocardiography, apoptosis index by terminal deoxynucleotidyl transferase dUTP nick-end labeling assessment and vascular development by immunohistochemical staining. The findings demonstrated that injection of bFGF along with hydrogel induced angiogenesis, reduced collagen content, MI area and cell apoptosis and improved cardiac function compared with the injection of either bFGF or hydrogel alone. bFGF incorporated with Dex-PCL-HEMA/PNIPAAm hydrogel injection induces angiogenesis, attenuates cardiac remodeling and improves cardiac function following MI.