Abstract
The aim of the study was to evaluate the clinical significance of microRNA-375 in acute myocardial infarction patients and its mimic action in hypoxia/reoxygenation- (H/R-) induced ventricular cardiomyocyte H9c2 injury. In the current study, 90 ST-elevated acute MI patients (STEMI), 75 non-ST-elevated acute MI patients (NSTEMI), 90 healthy subjects, 14 weeks old mice, and ventricular cardiomyocyte H9c2 were included. The expressions of plasma microRNA-375 in patients with STEMI and NSTEMI and AMI mouse models were remarkably decreased than in controls (P < 0.001). The areas under the curve (AUC) of plasma microRNA-375 were revealed 0.939 in STEMI and 0.935 in NSTEMI subjects. Moreover, microRNA-375 levels in H/R-exposed cardiac H9c2 cells were evidently downregulated and significantly increased apoptosis rate and caspase-3 activity levels, while overexpression of miR-375 remarkably reduced apoptosis percentage and caspase-3 levels as compared with normal cells. Furthermore, this study also demonstrated that Nemo-like kinase (NLK), NLK mRNA, and protein expression levels were significantly downregulated in H/R-injured H9c2 cells, on the contrary, H9c2 cells transfected with mimic-miR-375 greatly upregulated NLK mRNA and protein expression. Plasma microRNA-375 may serve as an essential clinical biomarker for diagnosis of early-stage AMI. Mimic expression of miR-375 significantly prevented H/R-induced cardiomyocyte injury by decreasing caspase-3 activity through upregulation of the NLK gene, recommended as a new therapeutic option for AMI patient.
Highlights
Acute myocardial infarction (AMI) or heart attack is the leading cause of sudden cardiac death all over the world
Glucose, highsensitivity C-reactive protein, LDH, and CK-MB levels were significantly elevated in ST-elevated acute MI patients (STEMI) and non-ST-elevated acute MI patients (NSTEMI) patients than in controls (P < 0:001)
The current study demonstrated that caspase-3 activity levels were highly expressed in hypoxia-reoxygenation H9c2 models than in controls
Summary
Acute myocardial infarction (AMI) or heart attack is the leading cause of sudden cardiac death all over the world. Cardiac-specific troponin T (cTnT) and troponin I (cTnI) are considered the “gold standard” biomarkers for the diagnosis of AMI patients. Currently, it was reported that high-sensitivity cardiac troponin is positive early after ischemia but serial testing is required because troponin is highly positive in patients with end-stage renal failure, heart failure, and chronic stable angina pectoris. Thrombolytic drugs such as a streptokinase, tenecteplase, and human tissue plasminogen activator have been widely used for the reperfusion therapy in acute myocardial infarction patients, but they have several complications and cannot be used in some selected patients. Discovering a new ideal drug for the management of all categories of AMI patients is required to reduce the mortality rate [4].
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