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Abstract Due to the cancer therapy-related cardiovascular toxicity, heart failure following cancer therapy has a significant mortality rate. Gene-targeted therapy promotes the re-entry of existing cardiomyocytes into the cell cycle to achieve myocardial regeneration, which is a promising strategy for preventing and treating heart failure after myocardial infarction. Circular RNAs (circRNAs) are considered as potential targets for myocardial regeneration due to their strong stability, resistance to degradation, and potential role in heart development and cardiovascular diseases. By comparing the myocardial tissue of mice in the sham operation group and the Doxorubicin therapy group (DOX), we observed a significant decrease in Cirsorbs expression in the DOX group. Cirsorbs was predominantly localized in cardiomyocytes and exhibited high conservation. Subsequent investigations revealed that Cirsorbs could promote myocardial proliferation and inhibit myocardial apoptosis. Mechanistic studies further demonstrated that Cirsorbs could bind to miR99 and reduce its expression level. Meanwhile, miR99 was found to bind to GATA4 mRNA and decrease its expression level. The binding of Cirsorbs to miR99 alleviated the repression of miR99, thereby enhancing GATA4 expression and the transcription of downstream cyclin A2 and cyclin E1. This, in turn, increased cardiomyocyte proliferation and reduced apoptosis. In conclusion, Cirsorbs holds promise as an effective target for myocardial regeneration in reducing cancer therapy-related cardiovascular toxicity.

Abstract Background Coronary heart disease (CHD) has become a worldwide public health problem. Genetic factors are considered important risk factors for CHD. The aim of this study was to explore the correlation between CYP4A22 gene polymorphism and CHD susceptibility in the Chinese Han population. Methods We used SNPStats online software to complete the association analysis among 962 volunteers. False-positive report probability analysis was used to confirm whether a positive result is noteworthy. Haploview software and SNPStats were used for haplotype analysis and linkage disequilibrium. Multi-factor dimensionality reduction was applied to evaluate the interaction between candidate SNPs. Results In overall and some stratified analyses (male, age ≤ 60 years or CHD patients complicated with hypertension), CYP4A22-rs12564525 (overall, OR = 0.83, p-value is 0.042) and CYP4A22-rs2056900 (overall, OR = 1.22, p-value is 0.032) were associated with the risk of CHD. CYP4A22-4926581 was associated with increased CHD risk only in some stratified analyses. FPRP indicated that all positive results in our study are noteworthy findings. In addition, MDR showed that the single-locus model composed of rs2056900 is the best model for predicting susceptibility to CHD. Conclusion There are significant associations between susceptibility to CHD and CYP4A22 rs12564525, and rs2056900.

Enhancing cardiomyocyte proliferation is essential to reverse or slow down the heart failure progression in many cardiovascular diseases such as myocardial infarction (MI). Long non-coding RNAs (lncRNAs) have been reported to regulate cardiomyocyte proliferation. In particular, lncRNA urothelial carcinoma-associated 1 (lncUCA1) played multiple roles in regulating cell cycle progression and cardiovascular diseases, making lncUCA1 a potential target for promoting cardiomyocyte proliferation. However, the role of lncUCA1 in cardiomyocyte proliferation remains unknown. This study aimed at exploring the function and underlying molecular mechanism of lncUCA1 in cardiomyocyte proliferation. Quantitative RT-PCR showed that lncUCA1 expression decreased in postnatal hearts. Gain-and-loss-of-function experiments showed that lncUCA1 positively regulated cardiomyocyte proliferation in vitro and in vivo. The bioinformatics program identified miR-128 as a potential target of lncUCA1, and loss of miR-128 was reported to promote cardiomyocyte proliferation by inhibiting the SUZ12/P27 pathway. Luciferase reporter assay, qRT-PCR, western blotting, and immunostaining experiments further revealed that lncUCA1 acted as a ceRNA of miR-128 to upregulate its target SUZ12 and downregulate P27, thereby increasing cyclin B1, cyclin E, CDK1 and CDK2 expression to promote cardiomyocyte proliferation. In conclusion, upregulation of lncRNA UCA1 promoted cardiomyocyte proliferation by inhibiting the miR-128/SUZ12/P27 pathway. Our results indicated that lncUCA1 might be a new therapeutic target for stimulating cardiomyocyte proliferation.

Abstract Purpose The research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk. Methods This case–control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection. Results As a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09–1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06–1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN). Conclusion This study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.

Abstract Background Coronary heart disease (CHD) is one of the most severe cardiovascular diseases. Cyclin‐dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B‐AS1) is a significant susceptibility locus for cardiovascular disease by regulating inflammation response and cell cycle. The aim of this study was to assess whether CDKN2B‐AS1 polymorphisms are associated with CHD risk in the Chinese Han population. Methods A total of 501 CHD patients and 496 healthy controls were recruited from Central South University Xiangya School of Medicine Affiliated Haikou Hospital, five CDKN2B‐AS1 polymorphisms (rs10115049, rs75227345, rs2383205, rs10738606, and rs1333049) were analyzed by the Agena MassARRAY platform. The association of CDKN2B‐AS1 polymorphisms and CHD risk was determined by odd ratios (OR) and 95% confidence intervals (CI) using logistic regression. Results CDKN2B‐AS1 rs10738606 was significantly associated with CHD under codominant (p = .03), dominant (p = .019), recessive (p = .010), additive (p = .003), and allele (p = .003) models. Gender‐based subgroup tests showed that four polymorphisms (rs75227345, rs2383205, rs10738606 and rs1333049) were associated with CHD in males (p