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The role of circulating miRNAs in diagnosis of acute myocardial infarction and the pathological significance
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摘要
Objectives: We aimed to explore the diagnostic value of circulating miRNAs(miR-149, miR-208 b, miR-378, miR-424, miR-499 and miR-765) in AMI patients, and protective role of miR-208 b or miR-378 or metoprolol during H/R injury in H9c2 cell with their underlying mechanisms. Methods: 205 AMI patients and 85 healthy subjects, twelve week-old C57BL/6 mice AMI and H9c2 cells were included in this study. Total RNA was isolated from plasma and cardiac cell with TRIzol reagent. Circulating miRNAs levels were measured by quantitative real-time polymerase chain reaction. Results: We found that miR-208 b, miR-499 and miR-765 levels were significantly up-regulated by 9.6 fold, 5.2 fold, and 5.1 fold in AMI patients compared with healthy subjects(p<0.001). Plasma miR-149, miR-378 and miR-424 levels were markedly downregulated by 5.5 fold, 4.9 fold and 5 fold in AMI patients compared with controls(p<0.001). Plasma levels of these miRNAs were returned towards normal at 96 h after PCI(p<0.001). We also found that plasma miR-208 b, miR-499 and miR-765 levels were significantly elevated by 11.5 fold, 3.9 fold, and 4.7 fold, while miR-149, miR-378 and miR-424 levels were noticeably decreased by 3.7 fold, 4.1 fold and 3.8 fold in Mice AMI compared with controls(p<0.001). The ROC curves of plasma miR-208 b, miR-499, miR-765, miR-149, miR-378 and miR-424 represented a strong discrimination between AMI patients and healthy subjects, with an area under curve(AUC) of 0.974, 0.971, 0.965, 0.963 0.969 and 0.973, respectively. Conclusions: Our findings suggested that miR-208 b, miR-499, miR-765, miR-149, miR-378, miR-424 may be used as a novel and sensitive diagnostic biomarker for AMI patients. Inhibition of miR-208 b and overexpression of miR-378 were effectively protected cardiomyocyte damage during H/R injury through their potential targets NLK and TRAF6, represents a new therapeutic approach for ischemic heart disease. Furthermore, metoprolol protected cardiomyocytes damage against H/R injury by suppressing oxidative stress.
Objectives: We aimed to explore the diagnostic value of circulating miRNAs(miR-149, miR-208 b, miR-378, miR-424, miR-499 and miR-765) in AMI patients, and protective role of miR-208 b or miR-378 or metoprolol during H/R injury in H9c2 cell with their underlying mechanisms. Methods: 205 AMI patients and 85 healthy subjects, twelve week-old C57BL/6 mice AMI and H9c2 cells were included in this study. Total RNA was isolated from plasma and cardiac cell with TRIzol reagent. Circulating miRNAs levels were measured by quantitative real-time polymerase chain reaction. Results: We found that miR-208 b, miR-499 and miR-765 levels were significantly up-regulated by 9.6 fold, 5.2 fold, and 5.1 fold in AMI patients compared with healthy subjects(p<0.001). Plasma miR-149, miR-378 and miR-424 levels were markedly downregulated by 5.5 fold, 4.9 fold and 5 fold in AMI patients compared with controls(p<0.001). Plasma levels of these miRNAs were returned towards normal at 96 h after PCI(p<0.001). We also found that plasma miR-208 b, miR-499 and miR-765 levels were significantly elevated by 11.5 fold, 3.9 fold, and 4.7 fold, while miR-149, miR-378 and miR-424 levels were noticeably decreased by 3.7 fold, 4.1 fold and 3.8 fold in Mice AMI compared with controls(p<0.001). The ROC curves of plasma miR-208 b, miR-499, miR-765, miR-149, miR-378 and miR-424 represented a strong discrimination between AMI patients and healthy subjects, with an area under curve(AUC) of 0.974, 0.971, 0.965, 0.963 0.969 and 0.973, respectively. Conclusions: Our findings suggested that miR-208 b, miR-499, miR-765, miR-149, miR-378, miR-424 may be used as a novel and sensitive diagnostic biomarker for AMI patients. Inhibition of miR-208 b and overexpression of miR-378 were effectively protected cardiomyocyte damage during H/R injury through their potential targets NLK and TRAF6, represents a new therapeutic approach for ischemic heart disease. Furthermore, metoprolol protected cardiomyocytes damage against H/R injury by suppressing oxidative stress.
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