Conclusions
These findings provide novel insights into the molecular mechanisms by which miR-let-7a and NGF contribute to the progression of sympathetic nerve remodeling after MI. Therefore, miR-let-7a may be a promising therapeutic target to reduce the incidence of arrhythmia following MI.
Objective
Sympathetic hyperinnervation following myocardial infarction (MI) is one of the primary causes of ventricular arrhythmias (VAs) after MI. Nerve growth factor (NGF) is a key molecule that induces sympathetic nerve remodeling. Previous studies have confirmed that microRNA (miR)-let-7a interacts with NGF. However, whether miR-let-7a is involved in sympathetic remodeling after MI remains unknown. We aimed to investigate whether miR-let-7a was associated with the occurrence of VA after MI.
Results
A rat model of myocardial infarction was established using left coronary artery ligation. miR-let-7a expression levels were analyzed by reverse transcription-quantitative PCR. Western blotting was also used to examine NGF expression levels in vivo and in M1 macrophages in vitro. The relationship between miR-let-7a and NGF levels was investigated using a luciferase reporter assay. The results revealed that the expression of miR-let-7a decreased significantly after MI, while NGF expression was significantly upregulated. In addition, overexpression of miR-let-7a effectively inhibited NGF expression in rats, which was also verified in M1 macrophages. Tyrosine hydroxylase and growth-associated protein 43 immunofluorescence results revealed that the administration of a miR-let-7a overexpression lentivirus to rats inhibited sympathetic remodeling after MI. Programmed electrical stimulation, renal sympathetic nerve activity recording, and heart rate variability measurements showed that miR-let-7a overexpression decreased sympathetic activity. Conclusions: These findings provide novel insights into the molecular mechanisms by which miR-let-7a and NGF contribute to the progression of sympathetic nerve remodeling after MI. Therefore, miR-let-7a may be a promising therapeutic target to reduce the incidence of arrhythmia following MI.