BackgroundmicroRNAs (miRNAs) post‐transcriptionally regulate cardiac repair following myocardial infarction (MI). Omega‐3 polyunsaturated fatty acid (ω‐3 PUFAs) may support cardiac healing after MI, but the mechanism is unclear.MethodsThe fat‐1 transgenic mouse expresses a ω‐3 fatty acid desaturase which converts ω‐6 PUFAs to ω‐3 PUFAs in vivo. MI was induced in fat‐1 transgenic (n = 30) and wild‐type (WT) mice (n = 30) using permanent ligation. Other transgenic and WT mice underwent sham procedure (n = 30 and n = 30, respectively). One week after occlusion, cardiac function was measured by echocardiography and the infarct size was assessed using histology and miRNA microarray profiling. Expression of selected miRNA was confirmed using quantitative real‐time PCR.ResultsOne week following MI, the fat‐1 transgenic myocardium had better cardiac function, a smaller fibrotic area, and fewer apoptotic cardiomyocytes than WT myocardium. Post‐MI profiling showed 33 miRNAs that were significantly up‐regulated, and 35 were down‐regulated, in fat‐1 group compared to the WT group (n = 3 and n = 2 mice, respectively). Among selected apoptosis‐associated miRNAs, 9 miRNAs were up‐regulated (miR‐101a‐3p, miR‐128‐3p,miR‐133a‐5p,miR‐149‐5p,miR‐192‐5p,miR‐1a‐3p,miR‐208a‐3p,miR‐29c‐5p,miR‐30c‐2‐3p), and 3 were down‐regulated (miR‐210‐3p,miR‐21a‐3p,miR‐214‐3p) in fat‐1 transgenic mice compared with WT mice. Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated likely roles for these miRNAs in MI. Furthermore, Bcl‐2 expression was increased, and caspase‐3 decreased, in infarcted fat‐1 transgenic mouse hearts compared to WT hearts.Conclusionsω‐3 PUFAs may have a protective effect on cardiomyocytes following MI through their modulation of apoptosis‐related miRNAs and target genes.

Background Although several meta‐analyses have examined the effects of off‐label underdosing of nonvitamin K antagonist oral anticoagulants (NOACs) compared with their recommended doses in patients with atrial fibrillation (AF), they combined different kinds of NOACs in their primary analyses. Herein, we first conducted a meta‐analysis to separately assess the effects of off‐label underdosing versus on‐label dosing of four individual NOACs on adverse outcomes in the AF population. Methods The PubMed and Embase database were systemically searched until November 2021 to identify the relevant studies. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by utilizing a random‐effects model. Results A total of nine studies with 144,797 patients taking NOACs were included in the meta‐analysis. In the pooled analysis, off‐label underdosing of rivaroxaban was related to an increased risk of stroke or systemic embolism (HR = 1.31, 95% CI 1.05–1.63; p = .02), whereas off‐label underdosing of apixaban was associated with a higher risk of all‐cause death (HR = 1.21, 95% CI 1.05–1.40; p = .01). When comparing off‐label underdosing versus on‐label dosing of dabigatran or edoxaban, no differences were found in the primary and secondary clinical outcomes. Conclusion Off‐label underdosing of rivaroxaban may increase the risk of stroke or systematic embolism, whereas off‐label underdosing of apixaban may heighten the incidence of all‐cause death.

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