Key result
MiR-874 antagomiR inhibited caspase-8 activity in cardiac fibroblasts and down-regulated MMP9 mRNA levels, while miR-146a mimics lowered calcium concentration in cardiomyocytes.
Why the study?
Although miR-874 inhibitors can reduce cardiomyocyte necrosis and may offer therapeutic value in heart failure, other effects of miR-874 and miR-146a on key pathways in cardiomyocytes and cardiac fibroblasts remained to be evaluated.
miR-874 antagomiR and miR-146a modulate specific pathways in cardiomyocytes and fibroblasts, suggesting potential therapeutic effects and side effects for heart failure treatment.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for miR-874/miR-146a in cardiac fibrosis and calcium handling; further preclinical validation required before clinical exploration.
More and more studies have shown that microRNAs (miRNAs) play key roles in the treatment of heart failure. Studies have shown that miR-874 (miR-874) inhibitors can reduce H 2 O 2 -induced cardiomyocyte necrosis and may have a therapeutic effect on heart failure in terms of cardiomyocyte necrosis. Therefore, the purpose of this experiment is to study the other effects of miR-874 and miR-146a on the key pathways in cardiomyocytes and cardiac fibroblasts. In this study, the roles of miR-874 antagomiR and miR-146a in cardiomyocytes and cardiac fibroblasts were analyzed. we investigated the level of miR-874 expression in H9C2 cardiomyocytes after miR-874 antagomiR transfection and found that the miR-874 expression in the H9C2 cells transfected with miR-874 antagomiR group was significantly lower than that in the control group. The results showed that miR-874 was successfully knocked down by the transfection of miR-874 antagomiR. Our results demonstrated that miR-874 inhibition has no effect on the activity of Caspase-3/7 in cardiomyocytes. miR-874 antagomiR has no effect on the proliferation of cardiac fibroblasts, whereas it can inhibit the activity of caspase-8 in cardiac fibroblasts. In addition, the potential effect of miR-874 antagomiR on cardiac remodeling associated genes were examined. miR-874 antagomiR had no effect on SERCA2a mRNA level in H9C2 cells. In addition, miR-874 antagomiR were able to down-regulate the mRNA level of MMP9 and had no effect on MMP2 mRNA levels in H9C2 cells. Finally, The concentration of Ca 2+ was measured using Fluo-4 NW Calcium Assay Kits following transfection of miRNAs or negative control in primary cardiomyocytes. miR-874 antagomiR was found to have no effect on Ca 2+ concentration in cardiomyocytes. the concentration of Ca 2+ in the cardiomyocytes transfected with miR-146a mimics was significantly lower than the mimic negative control group. In summary, miR-874 antagomiR and miR-146a may have a therapeutic effect on heart failure, but may also have side effects on heart failure treatment. Therefore, miR-874 antagomiR should be further studied to provide a basis for the development of drugs for heart failure.
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Guo et al. (2020) studied Heart failure (in vitro model). miR-874 antagomiR and miR-146a mimics vs. Negative control / mimics control was evaluated on Caspase-8 activity in cardiac fibroblasts (p=0.001). MiR-874 antagomiR inhibited caspase-8 activity in cardiac fibroblasts and down-regulated MMP9 mRNA levels, while miR-146a mimics lowered calcium concentration in cardiomyocytes.
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