Cardioprotective Role of Melatonin in Acute Myocardial Infarction

Abstract

Melatonin is a pleiotropic, indole secreted, and synthesized by the human pineal gland. Melatonin has biological effects including anti-apoptosis, protecting mitochondria, anti-oxidation, anti-inflammation, and stimulating target cells to secrete cytokines. Its protective effect on cardiomyocytes in acute myocardial infarction (AMI) has caused widespread interest in the actions of this molecule. The effects of melatonin against oxidative stress, promoting autophagic repair of cells, regulating immune and inflammatory responses, enhancing mitochondrial function, and relieving endoplasmic reticulum stress, play crucial roles in protecting cardiomyocytes from infarction. Mitochondrial apoptosis and dysfunction are common occurrence in cardiomyocyte injury after myocardial infarction. This review focuses on the targets of melatonin in protecting cardiomyocytes in AMI, the main molecular signaling pathways that melatonin influences in its endogenous protective role in myocardial infarction, and the developmental prospect of melatonin in myocardial infarction treatment.

Keywords: cardiomyocyte; cardioprotective; melatonin; mitochondrion; myocardial infarction.

FIGURE 1

A summary of the mechanisms that myocardial protection mediated by melatonin through receptor and non-receptor pathways. Melatonin has a biological role mainly by being bound to receptors. There are three downstream signal pathways of MT1/2, namely MAPK-ERK signal pathway, AMP-dependent protein kinase (AMPK) signal pathway and PI3K-Akt signal pathway. Melatonin also activates STAT3, a signal transducer and activator of transcription factor for antioxidant enzymes, by activating SAFE pathway. Besides, melatonin activates the Notch1 pathway, thus inhibiting PIK3 function. These downstream signaling molecules are crossed and connected within the cell. In addition, melatonin also enters cells where it has direct biological effects. It promotes the release of NO, enhances the activity of iNOS and boosts the expression of SIRT3 via the activation of PKB-Akt. The ultimate effects of these responses are to reduce oxidative stress, inflammatory responses, and to protect mitochondrial function, thereby reducing cardiomyocyte apoptosis.