Melatonin improves cardiac remodeling and brain–heart sympathetic hyperactivation aggravated by light disruption after myocardial infarction

Abstract

Light in the external environment might affect cardiovascular function. The light disruption seems to be related to changes in cardiovascular physiological functions, and disturbing light may be a risk factor for cardiovascular diseases. Prior studies have found that light disruption after myocardial infarction (MI) exacerbates cardiac remodeling, and the brain‐heart sympathetic nervous system may be one of the key mechanisms. However, how to improve light‐disrupted cardiac remodeling remains unclear. Melatonin is an indoleamine secreted by the pineal gland and controlled by endogenous circadian oscillators within the suprachiasmatic nucleus, which is closely associated with light/dark cycle. This study aimed to explore whether melatonin could improve light‐disrupted cardiac remodeling and modulate the brain‐heart sympathetic nervous system. Our study revealed that light disruption reduced serum melatonin levels, aggravated cardiac sympathetic remodeling, caused overactivation of the brain‐heart sympathetic nervous system, exacerbated cardiac dysfunction, and increased cardiac fibrosis after MI, while melatonin treatment improved light disruption‐exacerbated cardiac remodeling and brain‐heart sympathetic hyperactivation after MI. Furthermore, RNA‐Seq results revealed the significant changes at the cardiac transcription level. In conclusion, melatonin may be a potential therapy for light‐disrupted cardiac remodeling.

Circadian light/dark cycle reversal exacerbates the progression of chronic kidney disease in mice

“…In addition to β-NMN, melatonin, another renowned circadian regulator that has been considered the primary pharmacologic therapy for circadian disruption-associated symptoms, 45,46 can also offer therapeutic benefits in mitigating the adverse effects of light disruption on kidney function. 32,33,47 Although our findings align with the protective effects of melatonin and β-NMN observed in various circadian disruptionrelated pathological processes, 23,35,48,49 following studies are still necessary to further elucidate their detailed renal-protective mechanisms.…”

“…Mechanistically, several studies have suggested a close association between circadian disruption and enhanced release of adrenal catecholamines and RAAS activation 35–38 . In our investigation, we examined the serum levels of several hormones, including epinephrine, noradrenaline, angiotensin II, aldosterone, and corticosterone.…”

“…Mechanistically, several studies have suggested a close association between circadian disruption and enhanced release of adrenal catecholamines and RAAS activation. [35][36][37][38] In our investigation, we examined the serum levels of several hormones, including epinephrine, noradrenaline, angiotensin II, aldosterone, and corticosterone. Surprisingly, our results indicate that neither weekly LDDL nor the 6 h phase advance shifts had significant effects on these hormone levels (data not shown).…”

Essential Hypertension and Oxidative Stress: Novel Future Perspectives

“…The link between antioxidants and cardiovascular physiology has a rather long history, but only recently has more space been given to the clinical meaning and relevance that this relationship may have. Specifically, among the antioxidants, special attention was given to melatonin, according to its antihypertensive, antioxidant, and vasoprotective effects [40,41]. The main point was the possibility of acting on the morphostructural alterations induced by EH, improving in the short and long term the expectation and quality of life of the patients involved [5,42,43].…”

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure

“…The elevated damage seems to be a result of stimulation of the brain-heart sympathetic nervous system axis, which exaggerates the size of the infarct area with the development of fibrosis. Supplementation with melatonin overcame much of the cardiac injury by reversing cardiac remodeling, probably due to the suppression of the brain-heart sympathetic hyperactivation [70]. In a rat model of metabolic syndrome, orally administered melatonin beneficially modulated the electrical activity of the heart (normalizing the QT interval) as well as the left ventricular expression of KCNK and KVNH2 genes, both of which encode cardiac potassium ion channels [71].…”