Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating <scp>PGC</scp>‐1β: In vivo and in vitro studies

Background Melatonin is a multifunctional indolamine and has a cardioprotective role in a variety of cardiovascular processes via antioxidant, anti‐inflammatory, antihypertensive, antithrombotic, and antilipemic effects. It has been reported that lower levels of circulating melatonin are significantly associated with a higher risk of acute myocardial infarction (AMI) and later cardiac remodeling. However, levels of melatonin in patients with dilated cardiomyopathy (DCM) and associations between melatonin levels and cardiac function remain unclear. Methods and Results We measured and compared plasma levels of melatonin in 61 control subjects, 81 AMI patients, and 77 DCM patients. Plasma levels of melatonin were progressively decreased from 71.9 pg/mL in the control group to 52.6 pg/mL in the DCM group and 21.9 pg/mL in the AMI group. Next, we examined associations of melatonin levels with parameters of laboratory data, echocardiography, and right‐heart catheterization. In the DCM patients, circulating melatonin showed significant correlations with both high‐sensitivity troponin T ( R = −0.422, P < 0.001) and cardiac output ( R = 0.431, P = 0.003), but not with B‐type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), pulmonary artery wedge pressure, or pulmonary artery pressure. Conclusion Patients with not only AMI but also DCM had lower circulating melatonin levels. Circulating melatonin levels appear to correlate with myocardial injury and cardiac output in DCM patients.

Section: Discussionmentioning

confidence: 99%

Plasma levels of melatonin in dilated cardiomyopathy

Misaka

Yoshihisa

Yokokawa

et al. 2019

“…Melatonin, chemically N‐acetyl‐5‐methoxytryptamine, has been proved to exert its protective properties in a variety of cardiovascular diseases . Recent studies have reported that melatonin has the ability to protect against diabetes‐induced cardiac dysfunction .…”

Section: Introductionmentioning

confidence: 99%

“…Melatonin, chemically N-acetyl-5-methoxytryptamine, has been proved to exert its protective properties in a variety of cardiovascular diseases. [11][12][13][14][15] Recent studies have reported that melatonin has the ability to protect against diabetesinduced cardiac dysfunction. 16,17 Our previous study demonstrated that melatonin alleviated posttraumatic myocardial injury and cardiac dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Melatonin prevents Drp1‐mediated mitochondrial fission in diabetic hearts through SIRT1‐PGC1α pathway

Ding

Feng

Tang

et al. 2018

Self Cite

284

205

Myocardial contractile dysfunction is associated with an increase in mitochondrial fission in patients with diabetes. However, whether mitochondrial fission directly promotes diabetes‐induced cardiac dysfunction is still unknown. Melatonin exerts a substantial influence on the regulation of mitochondrial fission/fusion. This study investigated whether melatonin protects against diabetes‐induced cardiac dysfunction via regulation of mitochondrial fission/fusion and explored its underlying mechanisms. Here, we show that melatonin prevented diabetes‐induced cardiac dysfunction by inhibiting dynamin‐related protein 1 (Drp1)‐mediated mitochondrial fission. Melatonin treatment decreased Drp1 expression, inhibited mitochondrial fragmentation, suppressed oxidative stress, reduced cardiomyocyte apoptosis, improved mitochondrial function and cardiac function in streptozotocin (STZ)‐induced diabetic mice, but not in SIRT1−/− diabetic mice. In high glucose‐exposed H9c2 cells, melatonin treatment increased the expression of SIRT1 and PGC‐1α and inhibited Drp1‐mediated mitochondrial fission and mitochondria‐derived superoxide production. In contrast, SIRT1 or PGC‐1α siRNA knockdown blunted the inhibitory effects of melatonin on Drp1 expression and mitochondrial fission. These data indicated that melatonin exerted its cardioprotective effects by reducing Drp1‐mediated mitochondrial fission in a SIRT1/PGC‐1α‐dependent manner. Moreover, chromatin immunoprecipitation analysis revealed that PGC‐1α directly regulated the expression of Drp1 by binding to its promoter. Inhibition of mitochondrial fission with Drp1 inhibitor mdivi‐1 suppressed oxidative stress, alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. These findings show that melatonin attenuates the development of diabetes‐induced cardiac dysfunction by preventing mitochondrial fission through SIRT1‐PGC1α pathway, which negatively regulates the expression of Drp1 directly. Inhibition of mitochondrial fission may be a potential target for delaying cardiac complications in patients with diabetes.

“…Melatonin exhibits a repertoire of biological functions . It has been shown to influence immune function, tumor growth, sleep‐wake cycle and circadian rhythms and provide redox homeostasis and antioxidant protection in tissues .…”

Section: Discussionmentioning

confidence: 99%

“…Melatonin exhibits a repertoire of biological functions. 47 It has been shown to influence immune function, tumor growth, sleep-wake cycle and circadian rhythms and provide redox homeostasis and antioxidant protection in tissues. [23][24][25] Moreover, a number of studies demonstrated that melatonin is implicated in the development of scoliosis.…”

Section: Melatonin Protected Against the Detrimental Effects Of Mirmentioning

confidence: 99%

Melatonin protected against the detrimental effects of microRNA‐363 in a rat model of vitamin A‐associated congenital spinal deformities: Involvement of Notch signaling

et al. 2019

Congenital spinal deformities are a result of defective somitogenesis and are associated with vitamin A deficiency (VAD). However, the molecular mechanisms of VAD‐associated congenital spinal deformities remain largely unknown. Increasing number of studies suggested that microRNAs and melatonin played important roles in the development of congenital spinal deformities. In this study, we showed that the whole‐embryo expression of miR‐363 was upregulated in VAD rats. Furthermore, we demonstrated that miR‐363 inhibited the proliferation and neuronal differentiation of primary cultured NSCs, accompanied by downregulation of Notch1. To this end, melatonin suppressed miR‐363 expression and rescued the effects of miR‐363 on NSC proliferation and neuronal differentiation together with restoration of Notch signaling. The present study provided new insights into the mechanism of VAD‐associated spinal deformities and the therapeutic effect of melatonin that may lead to novel understanding of the molecular mechanisms of congenital spinal deformities.