miR-let-7a inhibits sympathetic nerve remodelling after myocardial infarction by downregulating the expression of nerve growth factor
Research Square (Research Square)(2023)
摘要
Abstract Objective Sympathetic hyperinnervation following myocardial infarction (MI) is a one of the primary causes of ventricular arrhythmias (VAs) after MI. Nerve growth factor (NGF) is a key molecule that induces sympathetic nerve remodelling. Previous studies have confirmed that microRNA (miR)-let-7a interacts with NGF. However, whether miR-let-7a is involved in sympathetic remodelling after MI remains unknown. Our aim was to investigate whether miR-let-7a was associated with the occurrence of VA after MI. Methods and Results A rat model of myocardial infarction was established using left coronary artery ligation. miR-let-7a expression levels were analysed 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 remodelling 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 remodelling after MI. Therefore, miR-let-7a may be a promising therapeutic target to reduce the incidence of arrhythmia following MI.
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关键词
myocardial infarction,sympathetic nerve remodelling,mir-let
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