Differential expression of exosomal circRNAs and regulatory framework genes in myocardial infarction patients with cardiac remodeling in response to Tongguan Capsules

Objective:Cardiac remodeling when myocardial infarction(MI)is achieved is an established prognostic factor for function-related damage and failure of hear that happen progressively.Tongguan Capsules(TGC),i.e.,a Chinese herbal treatment with patent has been previously demonstrated its potential benefits in cardiac function,but little is known about related mechanisms.This study sought to isolate and characterize exosomal circRNA profiles from post-MI cardiac remodeling patients in response to TGC,and further explore the possible molecular mechanisms.Methods:Exosomes were isolated from the plasma and analyzed by the detection of protein marker expression and transmission electron microscopy.This study employed DESeq2 package within Bioconductor for exploring circRNAs and determining the circRNA with differential expressions.Co-expression investigation was performed with the use of a weighted correlation framework.An investigation was conducted on the molecular framework and channels of different circRNA based on the investigation system of the and Kyoto Encyclopedia of Genes and Genomes(KEGG)Gene Ontology(GO)channels.The prediction was conducted for circRNA-miRNA interactions on the basis of frequently employed target prediction software,and the framework was built with the use of Cytoscape software.Results:In total,33084 circRNAs were detected in all chromosomes and 10065 circRNAs were identified with the use of circBase.Of them,40,207 and 258 differentially expressed circRNAs were detected between the MI group and control,MI and TGC groups,and the control and TGC groups.The differentially expressed circRNAs between the MI group and control,MI group and TGC group,and control and TGC group were significantly enriched in microtubule nucleation(BP,GO:0007020),protein binding(MF,GO:0005515),regulation of natural killer cell mediated cytotoxicity(BP,GO:0042269)corresponding to the cell cycle(hsa04110),lysine degradation(hsa00310)and lysine degradation(hsa00310)in KEGG channel investigation.Module_darkorange2 indicated the most differentiation with other modules by WGCNA investigation.This study employed a total of 14 circRNAs and 8 miRNAs which have significant interactions with each other for building the circRNA-miRNA frameworks,which indicated that has-miR-619-5p,has-miR-1268a and hasmiR-1285‐3p were under the regulation of a higher amount of circRNAs as compared with other miRNAs.Conclusion:In conclusion,different mechanisms and channels participated in the pathological processes associated with cardiac remodeling following MI.The altered circRNAs are likely to be critical to the cardioprotection of TGC through the circRNA-miRNA frameworks.

Effects of Tongguan Capsule(通冠胶囊)on Post-myocardial Infarction Ventricular Remodeling and Cardiac Function in Rats

Objective：To observe the effects of Tongguan Capsule（通冠胶囊,TGC） on post-myocardial infarction ventricular remodeling and heart function in rats.Methods：A rat model of acute myocardial infarction （AMI） was established by coronary ligation.Experimental rats were randomized to 4 groups including three model groups（Group A：captopril 5 mg/kg·day,n=7;Group B：TGC 10 g/kg·day,n=7;and Group C：placebo, n=8）,and a sham-control group（Group D：blank control,n=6）.Animals were treated for 4 weeks.The cardiac function of rats was assessed at the end of the experiment based on left ventricular ejection fraction（LVEF） and left ventricular short axis fractional shortening（LVFS） detected by colored echocardiography;meanwhile, the condition of ventricular remodeling was observed through the levels of left ventricular mass（LVM）,plasma aldosterone（ALD）,myocardial angiotensinⅡ（AngⅡ） and myocardial collagen measurements.Results：At the end of the experiment,LVEF and LVFS in Group A and B were improved significantly,while those in Group C were unchanged,the LVEF in Group A,B,C,and D was 0.57±0.46,0.61±0.08,0.36±0.55 and 0.76±0.02,respectively;and their LVFS was 0.31±0.52,0.34±0.04,0.23±0.57 and 0.45±0.03,respectively.The difference was statistically significant when comparing the two indexes in Group A and B with those in Group C and D（P〈0.05）.LVM,levels of plasma ALD and myocardial AngⅡwere lower in Group A and B than in Group C,but a comparison between Group A and B showed an insignificant difference in lowering LVM and ALD,while the lowering of AngⅡwas more significant in Group B than in Group A（754.7±18.7 pg/mL vs 952.6±17.6 pg/ mL,P〈0.05）.Morphological examination showed that in Group A and B the swollen myocardial cells had shrunk, with regularly arranged myocardial fibers and decreased collagen proliferation,but the improvements in Group B were more significant.Conclusion：TGC could markedly improve the post-infarction ventricular remodeling and cardiac function in rats,showing that the efficacy was better than or equal to that of captopril.

Effect of Tongguan Capsules(通冠胶囊) on Restenosis after Coronary Stent Implantation:Study Protocol for A Randomized Controlled Trial

Background:Although percutaneous coronary intervention(PCI)had become widely employed therapeutic procedure for coronary artery disease,stent restenosis limited the benefits of this revascularization and the question how to prevent such events remained unresolved.While numerous empirical observations suggested Tongguan Capsules(通冠胶囊),a patented Chinese Medicine,could decrease frequency and duration of angina pectoris attacks,evidence supporting its efficacy on restenosis remained inadequate.Objective:This trial was designed to determine whether Tongguan Capsules would reduce restenosis rate in patients after successful stent implantation.Methods:Approximately 400 patients undergoing percutaneous coronary stent deployment were enrolled and randomized to control group or Tongguan Capsules(4.5 g/d)for 3 months.All patients received standard anti-platelet,anti-coagulation and lipid-decreasing treatments,concurrently.The primary clinical endpoint was the 12-month incidence of the major adverse cardiovascular events(defined as cardiac death,myocardial infarction,and recurrence of symptoms requiring additional revascularization).The angiographic end point was restenosis rate at 6 months.Conclusion:This study would provide important evidence for the use of Tongguan Capsules in patients after stent implantation in combination with routine therapies,which may significantly reduce incidence of the restenosis so as to potentially improve the clinical outcomes.(registration number:ChiCTR-TRC-ChiCTR-IIR-17011407)