Introduction
Heart disease is complex and involves many risk factors. In this condition, the heart cannot pump enough blood to the body due to cardiac abnormalities in structure or function. Melatonin is an endocrine hormone released from the pineal gland. It has a role as a chronobiotic or endogenous in various cardiovascular pathologies and metabolic disorders.
What Is Melatonin?
Melatonin is a hormone released from the endocrine system and has a role in the sleep-wake cycle called the circadian rhythm. Other sources like the retina, gastrointestinal tract tissues, skin, platelets, and bone marrow secrete melatonin. It is formed from tryptophan via enzymatic reactions.
Melatonin is a natural hormone that has a role in cellular metabolism and apoptosis (death of cells as a normal process) and acts as an antioxidant and anti-inflammatory agent in the body.
Studies have shown that melatonin has a role in cardiovascular health, thereby reducing blood pressure and affecting endothelial function. Melatonin also regulates lipid and glucose metabolism and has a role in many cardiovascular diseases, including myocardial ischemia-reperfusion injury, atherosclerosis, hypertension, heart failure, and drug-induced myocardial injury.
People with heart failure will have many complications that need to be treated, which is as crucial as of treatment of heart failure. Muscle wasting or sarcopenia (muscle mass loss due to aging) are important complications of heart failure. Many studies have recently shown that melatonin has a role in treating heart diseases.
Heart diseases are considered a significant cause of death in the world. Around 17.9 million people die every year due to heart disease. Researchers have found that heart disease patients have less melatonin in their blood. There is an inverse relation, such as individuals with low melatonin levels are at higher risk of getting affected with heart diseases.
What Is the Role of Melatonin in Myocardial Ischemia-Reperfusion Injury?
Melatonin protects against ischemia-reperfusion injury in many organs like the heart, liver, and kidney. Melatonin acts on silent information regulator 1 (SIRTI) signals in a receptor-dependent manner. A study showed that melatonin protects adipose-derived mesenchymal stem cells (ADSCs) against hypoxia (reduced oxygen in the tissues). Melatonin treatment reduced the expression of apoptotic (cell death) proteins and increased the expression of antiapoptotic protein B-cell lymphoma 2 (BCL-2).
Melatonin can improve the survival and function of ADSCs. Increased expression of Copper-zinc superoxide dismutase (SOD-1), other antioxidant enzymes, and some growth factors produce protective effects. Endoplasmic reticulum stress is a contributing factor in cardiovascular diseases. Melatonin helps reduce endoplasmic reticulum stress by suppressing protein kinase ribonucleic acid-like endoplasmic reticulum kinase ( PERK) signaling.
Melatonin protects against ischemia-reperfusion injury through increased toll-like receptor 4 (TLR4) signaling and increases mitochondrial signal transducer and activator of transcription 3 (STAT-3) expression. This results in the activation of the survivor-activating enhancement pathway, which helps in protecting against ischemia-reperfusion injury.
How Does Melatonin Help in Myocardial Chronic Hypoxic Injury (CIH)?
Obstructive sleep apnea is related to CIH and increases the injury to muscles of the heart, leading to ischemic heart disease. A study showed that melatonin protects against CIH-induced myocardial inflammation, fibrosis, and ischemia-reperfusion injury. Treatment with melatonin reduced the expression of cytokines like tumor necrosis factor-alpha (TNF-alpha) and IL-6 (interleukin-6) and markers of fibrosis.
Melatonin treatment reduced the infarct size in hearts with ischemic reperfusion by lessening the effect of calcium (2+) homeostasis in cardiomyocytes and reducing the expression for enzymes (nicotinamide adenine dinucleotide phosphate oxidase (p22 and NOX2) and antioxidants enzymes).
Melatonin receptor agonists (Neu-p11) showed to reduce signaling and protect myocardial cells from hypoxia-reoxygenation injury. Cardiovascular diseases are related to mitochondrial dysfunction. Neu-p11 protected mitochondria in these diseases.
How Does Melatonin Treatment Help in Pulmonary Hypertension?
Elevated pulmonary arterial hypertension leads to ventricular hypertrophy and failure. Treatment of melatonin helped in reducing interstitial fibrosis and plasma oxidative stress in pulmonary hypertension. A study showed that melatonin improved vasodilatation of small pulmonary arteries, reduced pulmonary hypertension, increased nitric oxide bioavailability, and reduced pulmonary oxidative stress.
How Does Melatonin Help in Hypertension?
Continuous light exposure leads to hypertension, increased oxidative stress in the left ventricle and aorta, left ventricular hypertrophy, and left ventricle fibrosis. Melatonin helped treat these conditions, and decreasing renal oxidative stress and vascular reactivity helped reduce hypertension.
How Does Melatonin Help in Vascular Diseases?
Melatonin treatment helped reduce atheromatous plaques by changing mitogen-activated protein kinase (MAPK) pathway signal transduction. A recent study showed to decrease in aortic endothelial permeability and atherosclerosis. It also showed anti-inflammatory effects in restenosis (reduction in lumen diameter), improved vascular dysfunction, and micro or macrovascular diseases.
How Does Melatonin Help in Lipid Metabolism?
Dyslipidemia is a risk factor for heart disease. Melatonin reduces cholesterol, helps treat lipid metabolism and weight, and in turn, helps treat cardiovascular diseases. Melatonin also has a role in embryonic development by acting on the placenta and neuroglial cells as an antioxidant, acting on cell surface receptors, and reducing the generation of free radicles and reactive oxygen species (ROS). Melatonin acts as a natural antioxidant and scavenger. It is also involved in maintaining the immune system. The immune system and pineal gland work bidirectionally because cytokines, interleukins, and interferons-ˠ can affect the release and production of melatonin. It has been shown to have anticancer activity and the ability to protect against tumorigenesis. Observations suggested that melatonin's anti-cancer activity depends on the circadian cycle's stage.
Beta-blockers are given to hypertensive patients. These cause insomnia, which can be treated by giving melatonin supplements to improve sleep in these patients. Melatonin affects cardiac output, heart rate, blood pressure, and seasonal rhythms. Drug-induced cardiotoxicity can be treated by melatonin.
Conclusion:
Melatonin, a natural hormone, plays a significant role in cardiac disease treatment. It is mainly associated with the circadian rhythm, which is associated with many bodily functions. Recent advances in treating cardiac diseases are very challenging and must be potential to treat and must be safe. Melatonin has many effects on the human body. Hence, knowing about it is an added advantage in treating many severe diseases and helps identify the disease at the earliest and seek help from a doctor.
