Melatonin ameliorates myocardial infarction in obese diabetic individuals: The possible involvement of macrophage apoptotic factors

Abstract

In recent days, the hike in obesity-mediated epidemics across the globe and the prevalence of obesity-induced cardiovascular disease has become one of the chief grounds for morbidity and mortality. This epidemic-driven detrimental events in the cardiac tissues start with the altered distribution and metabolism pattern of high-density lipoprotein and low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on the arterial wall and atherosclerotic plaque generation, followed by vascular spasms and infarction. Subsequently, obesitytriggered metabolic malfunctions induce free radical generation which may further trigger pro-inflammatory signaling and nuclear factor kappa-light-chainenhancer of activated B cells transcriptional factor, thus inducing interferongamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase. This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby making obese diabetic patients prone toward the development of myocardial infarction (MI) or stroke in comparison to their nondiabetic counterparts. The accelerated oxidative stress and pro-inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals, causing progression of athero-thrombotic vascular disease. Being an efficient antioxidative and anti-inflammatory indolamine, melatonin effectively inhibits lipid peroxidation, pro-inflammatory reactions, thereby resolving free radical-induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterol concentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti-inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity-induced acute MI. This

Therapeutic strategies targeting mechanisms of macrophages in diabetic heart disease

“…Fiorina et al [ 206 ] showed that changes in melatonin secretion are related to the immune status of the body. In addition, melatonin may protect against cardiac complications in patients with DM by attenuating apoptotic pathways and addressing the inflammatory response and ROS burden by promoting macrophage polarization toward an anti-inflammatory state [ 207 ]. Further studies on melatonin-targeted regulation of macrophages in DHD should be explored.…”

Therapeutic Benefits of Melatonin against COVID-19

“…Moreover, being highly safe, accessible in abundance, and even cheap at cost, Cross et al [ 9 ] have recommended the administration of melatonin about 2.5–10 mg dose before sleep at night to all adults infected with SARS-CoV-2 immediately on the very first day of diagnosis, especially for the patients having comorbidities and higher mortality risk. Ample shreds of evidence as anti-cancerous [ 94 ], antioxidant, anti-inflammatory [ 95 ], and immunomodulatory prove that the effects of melatonin through the specific nuclear and plasma membrane melatonin receptors [ 96 ] can significantly deplete the gravity of symptoms and motility to cells caused by viral diseases when started as an early remedy. The pineal product melatonin strategically slows down the cytokine surge seen in COVID-19 subjects, reduces oxidized destruction to upgrade the resistive capabilities of patients and thus provides an increased life span.…”

The Dual Angiogenesis Effects via Nrf2/HO-1 Signaling Pathway of Melatonin Nanocomposite Scaffold on Promoting Diabetic Bone Defect Repair

“… 13 , 14 The antioxidant therapeutic effect of MT has been widely studied in pathological environments such as tumors and inflammation. 15 , 16 In recent years, some scholars have gradually paid attention to the antioxidant activity of MT in DM-related complications, 17 , 18 especially in bone lesions caused by diabetes. 19 , 20 Our previous study found that MT electrospun nanofiber coatings protect osteoblasts by inhibiting ROS overproduction and directly improving osteogenesis via the BMP/WNT pathway under diabetic conditions.…”