Evidence for the Benefits of Melatonin in Cardiovascular Disease

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: June 20, 2022

The pineal gland is a neuroendocrine which produces melatonin, hormone with critical physiological roles in the circadian rhythm and sleep-wake cycle. Melatonin has been shown to possess anti-oxidant activity neuroprotective properties. Numerous studies have that melatonin significant functions cardiovascular disease, may anti-aging ability of decrease primary hypertension needs be more extensively evaluated. benefits reducing cardiac pathology, preventing death muscle response ischemia-reperfusion rodent species. Moreover, also prevent hypertrophy heart under some circumstances, turn would lessen development failure. Several currently used conventional drugs show cardiotoxicity as an adverse effect. Recent acts effective suppressing damage mediated by pharmacologic drugs. Therefore, cardioprotective multiple animal human studies. Herein, we summarize most established system focus on molecular mechanisms action.

Language: Английский

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New insights into the role of mitochondrial metabolic dysregulation and immune infiltration in septic cardiomyopathy by integrated bioinformatics analysis and experimental validation

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Jan. 30, 2024

Abstract Background Septic cardiomyopathy (SCM), a common cardiovascular comorbidity of sepsis, has emerged among the leading causes death in patients with sepsis. SCM’s pathogenesis is strongly affected by mitochondrial metabolic dysregulation and immune infiltration disorder. However, specific mechanisms their intricate interactions SCM remain unclear. This study employed bioinformatics analysis drug discovery approaches to identify regulatory molecules, distinct functions, underlying metabolism microenvironment, along potential interventional strategies SCM. Methods GSE79962, GSE171546, GSE167363 datasets were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) module identified using Limma Weighted Correlation Network Analysis (WGCNA), followed functional enrichment analysis. Machine learning algorithms, including support vector machine–recursive feature elimination (SVM–RFE), least absolute shrinkage selection operator (LASSO) regression, random forest, used screen mitochondria-related hub for early diagnosis Subsequently, nomogram was developed based on six genes. The immunological landscape evaluated single-sample gene set (ssGSEA). We also explored expression pattern distribution mitochondria/inflammation-related pathways UMAP plots single-cell dataset. Potential drugs Drug Signatures Database (DSigDB). In vivo vitro experiments performed validate pathogenetic mechanism therapeutic efficacy candidate drugs. Results Six DEGs [MitoDEGs; translocase inner membrane domain-containing 1 (TIMMDC1), ribosomal protein S31 (MRPS31), F-box only 7 (FBXO7), phosphatidylglycerophosphate synthase (PGS1), LYR motif containing (LYRM7), chaperone BCS1 (BCS1L)] identified. diagnostic model demonstrated high reliability validity both training validation sets. microenvironment differed between control groups. Spearman correlation revealed that MitoDEGs significantly associated cells. Upregulated showed remarkably naive/memory B cell, CD14 + monocyte, plasma cell subgroup, evidenced plot. varied across subgroups individuals. Metformin predicted be most promising highest combined score. Its restoring function suppressing inflammatory responses been validated. Conclusions presents comprehensive SCM, providing novel direction medical intervention

Language: Английский

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SirT3 activates AMPK-related mitochondrial biogenesis and ameliorates sepsis-induced myocardial injury

Aging, Journal Year: 2020, Volume and Issue: 12(16), P. 16224 - 16237

Published: July 28, 2020

Sirtuin-3 (SirT3) and AMPK stimulate mitochondrial biogenesis, which increases turnover cardiomyocyte regeneration. We studied the effects of SirT3, AMPK, biogenesis on sepsis-induced myocardial injury. Our data showed that after treating cardiomyocytes with lipopolysaccharide, SirT3 levels decreased, this was followed by dysfunction death. Overexpression activated pathway improved is required to sustain redox balance, maintain respiration, suppress apoptosis. Inhibition abolished SirT3/AMPK-induced cardioprotection causing damage. These findings indicate reduces injury activating AMPK-related biogenesis.

Language: Английский

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Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice

Clinical and Translational Medicine, Journal Year: 2020, Volume and Issue: 10(5)

Published: Sept. 1, 2020

Abstract Background Sepsis remains a major health issue without an effective therapy. Ferroptosis, iron‐dependent programmed cell death, has been proposed to be related the pathogenesis of sepsis. Irisin, myokine released during exercise, improves mitochondrial function under various conditions. Ferroptosis is closely function. However, role irisin in sepsis‐induced ferroptosis and dysfunction liver remained unknown. Thus, we hypothesize that treatment suppresses Methods To study this, first explored serum levels patients with sepsis, then determined effect administration on septic mice. Results Serum were decreased negatively correlated APACHE II scores In mice subjected cecal ligation puncture (CLP), exogenous suppressed ferroptosis, inhibited inflammatory response, reactive oxygen species (ROS) production, restored abnormal morphology, increased mtDNA copy number adenosine triphosphate (ATP) content. The was confirmed LPS‐treated hepatocytes CLP‐induced Inhibition glutathione peroxidase 4 (GPX4), central regulator reduced irisin's protective effects mice, while blocking receptor RGD peptide or Echistain irisin‐induced GPX4 expression. Conclusions are disease severity restores experimental Irisin may offer therapeutic potential management

Language: Английский

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Involvement of GPX4 in irisin's protection against ischemia reperfusion‐induced acute kidney injury

Journal of Cellular Physiology, Journal Year: 2020, Volume and Issue: 236(2), P. 931 - 945

Published: June 24, 2020

Ischemia reperfusion (I/R)-induced acute kidney injury (AKI) is a common and serious condition. Irisin, an exercise-induced hormone, improves mitochondrial function reduces reactive oxygen species (ROS) production. Glutathione peroxidase 4 (GPX4) key regulator of ferroptosis its inactivation aggravates renal I/R by inducing ROS However, the effect irisin on GPX4 I/R-induced AKI still unknown. To study this, male adult mice were subjected to occluding bilateral hilum for 30 min, which was followed 24 hr reperfusion. Our results showed serum levels decreased in mice. Irisin (250 μg/kg) treatment alleviated injury, downregulated inflammatory response, improved function, reduced ER stress oxidative after I/R, associated with upregulation GPX4. Treated RSL3 (a inhibitor) abolished irisin's protective effect. Thus, attenuates through upregulating

Language: Английский

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Irisin alleviates LPS-induced liver injury and inflammation through inhibition of NLRP3 inflammasome and NF-κB signaling

Journal of Receptors and Signal Transduction, Journal Year: 2020, Volume and Issue: 41(3), P. 294 - 303

Published: Aug. 19, 2020

Lipopolysaccharide (LPS) provokes severe inflammation and cell death in sepsis, with liver being the major affected organ. Up-to-date, neither mechanism of action nor target treatment is readily available for LPS-induced injury. This study examined effect irisin, an endogenous hormonal peptide, on injury using animal models, involved a special focus pyroptosis. Irisin known to regulate glucose metabolism, inflammation, immune response, while our earlier work denoted anti-inflammatory anti-apoptotic properties irisin. Inflammatory factors AST/ALT were also detected. Pyroptosis, apoptosis, reactive oxygen species (ROS) evaluated PI staining, TUNEL DCFH-DA fluorescence, western blot, respectively. Our results indicated that irisin attenuated release inflammatory cytokines. Increased activity NLRP3 inflammasome was discovered LPS-challenged Raw264.7 cells, along elevated levels effects which mediated by activation ROS nuclear factor κB (NF-κB) signaling. These changes reversed following treatment. demonstrated countered LPS-mediated via inhibiting NF-κB findings revealed role as promising new anti-pyroptosis/apoptosis agent reconcile onset progression septic

Language: Английский

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Neuronal Mitochondria Modulation of LPS-Induced Neuroinflammation

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(8), P. 1756 - 1765

Published: Jan. 14, 2020

Neuronal mitochondria dysfunction and neuroinflammation are two prominent pathological features increasingly realized as important pathogenic mechanisms for neurodegenerative diseases. However, little attempt has been taken to investigate the likely interactions between them. Mitofusin2 (Mfn2) is a mitochondrial outer membrane protein regulating fusion, dynamic process essential function. To explore significance of neuronal in regulation neuroinflammation, male female transgenic mice with forced overexpression Mfn2 specifically neurons were intraperitoneally injected lipopolysaccharide (LPS), widely used approach model neurodegeneration-associated neuroinflammation. Remarkably, LPS-induced lethality was almost completely abrogated mice. Compared nontransgenic wild-type mice, also exhibited alleviated bodyweight loss, behavioral sickness, myocardial dysfunction. release IL-1β but not TNF-α further found greatly inhibited CNS overexpression, whereas peripheral inflammatory responses blood, heart, lung, spleen remained unchanged. At cellular molecular levels, suppressed activation microglia, prevented fragmentation neurons, importantly, upregulated expression CX3CL1, unique chemokine constitutively produced by suppress microglial activation. Together, these results reveal an unrecognized possible role activation, propose mechanistic linker neurodegeneration. SIGNIFICANCE STATEMENT Our study suggests that contributes Based on remarkable suppression abnormalities Mfn2, this centered Mfn2-mediated reveals novel involved both The pharmacological targeting may present treatment neuroinflammation-associated

Language: Английский

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[Retracted] Irisin Attenuates Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in the H9C2 Cellular Model of Septic Cardiomyopathy through Augmenting Fundc1‐Dependent Mitophagy

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

In the present study, we used lipopolysaccharide- (LPS-) stimulated H9C2 cardiomyocytes to investigate whether irisin treatment attenuates septic cardiomyopathy via Fundc1-related mitophagy. Fundc1 levels and mitophagy were significantly reduced in LPS-stimulated but increased by treatment. Irisin ATP production activities of mitochondrial complexes I III cardiomyocytes. also improved glucose metabolism LPS-induced reactive oxygen species increasing antioxidant enzymes, glutathione peroxidase (GPX), superoxide dismutase (SOD), as well (GSH). TUNEL assays showed that cardiomyocyte apoptosis suppressing activation caspase-3 caspase-9. However, beneficial effects on oxidative stress, metabolism, viability abolished silencing Fundc1. These results demonstrate abrogates dysfunction, through This suggests is a potentially useful for cardiomyopathy, though further investigations are necessary confirm our findings.

Language: Английский

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Melanin nanoparticles alleviate sepsis-induced myocardial injury by suppressing ferroptosis and inflammation

Bioactive Materials, Journal Year: 2022, Volume and Issue: 24, P. 313 - 321

Published: Dec. 27, 2022

Myocardial injury as one of the severe complications leads to increasing morbidity and mortality in patients with sepsis. Recent studies reported that reactive oxygen species (ROS)-mediated ferroptosis plays a critical role development heart diseases. Therefore, we hypothesized anti-ferroptosis agent might be novel potential therapeutic strategy for sepsis-induced cardiac injury. Herein, demonstrated small biocompatible MRI-visible melanin nanoparticles (MMPP) improves myocardial function by inhibiting ROS-related signaling pathway. In LPS-induced murine sepsis model, after single dose intravenously injection MMPP treatment, markedly alleviated including structure disorder through suppressing iron-accumulation induced ferroptosis. vitro, inhibited cardiomyocyte death attenuating oxidative stress, inflammation maintaining mitochondrial homeostasis. Collectively, our findings protected against via inflammation, which approach future.

Language: Английский

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Irisin, an exercise-induced bioactive peptide beneficial for health promotion during aging process

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 80, P. 101680 - 101680

Published: July 3, 2022

Language: Английский

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