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Microvascular obstruction (MVO) of coronary arteries promotes an increase in mortality and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). Intramyocardial hemorrhage (IMH) is observed in 41-50% of patients with ST-segment elevation myocardial infarction and PCI. The occurrence of IMH is accompanied by inflammation. There is evidence that microthrombi are not involved in the development of MVO. The appearance of MVO is associated with infarct size, the duration of ischemia of the heart, and myocardial edema. However, there is no conclusive evidence that myocardial edema plays an important role in the development of MVO. There is evidence that platelets, inflammation, Ca 2 + overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. The role of endothelial cell damage in MVO formation remains unclear in patients with AMI and PCI. It is unclear whether nitric oxide production is reduced in patients with MVO. Only indirect evidence on the involvement of inflammation in the development of MVO has been obtained. The role of reactive oxygen species (ROS) in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied. The significance of the balance of thromboxane A2, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is currently unknown. Conclusive evidence regarding the role of coronary artery spasm in the development of MVhasn't been established. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI has not previously been performed. It is unclear whether epinephrine aggravates reperfusion necrosis of cardiomyocytes. Dual antiplatelet therapy improves the efficacy of PCI in prevention of MVO. It is unknown whether epinephrine or L-type Ca 2 + channel blockers result in the long-term improvement of coronary blood flow in patients with MVO., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Melatonin has been reported to cause myocardial electrophysiological changes and prevent ventricular tachycardia or fibrillation (VT/VF) in ischemia and reperfusion. We sought to identify electrophysiological targets responsible for the melatonin antiarrhythmic action and to explore whether melatonin receptor-dependent pathways or its antioxidative properties are essential for these effects. Ischemia was induced in anesthetized rats given a placebo, melatonin, and/or luzindole (MT1/MT2 melatonin receptor blocker), and epicardial mapping with reperfusion VT/VFs assessment was performed. The oxidative stress assessment and Western blotting analysis were performed in the explanted hearts. Transmembrane potentials and ionic currents were recorded in cardiomyocytes with melatonin and/or luzindole application. Melatonin reduced reperfusion VT/VF incidence associated with local activation time in logistic regression analysis. Melatonin prevented ischemia-related conduction slowing and did not change the total connexin43 (Cx43) level or oxidative stress markers, but it increased the content of a phosphorylated Cx43 variant (P-Cx43 368 ). Luzindole abolished the melatonin antiarrhythmic effect, slowed conduction, decreased total Cx43, protein kinase Cε and P-Cx43 368 levels, and the IK1 current, and caused resting membrane potential (RMP) depolarization. Neither melatonin nor luzindole modified INa current. Thus, the antiarrhythmic effect of melatonin was mediated by the receptor-dependent enhancement of impulse conduction, which was associated with Cx43 phosphorylation and maintaining the RMP level.

Background: The prognostic value of ambulatory blood pressure (BP) monitoring (ABPM) is poorly understood in Latin American populations., Methods: A prospective observational study was conducted on 1339 patients with hypertension who underwent 24-h BP monitoring between 2015 and 2019. The incidence of serious adverse cardiovascular events (MACE) was analysed using a Cox proportional hazards model adjusted for potential confounders. Three previously reported morning surge definitions were evaluated for SBP and DBP using different ABPM components: sleep-through morning surge, pre-awakening, and morning night-time difference., Results: The mean age was 62 years, 52% were female, 32.8% had dyslipidaemia, 27.2% were smokers, and 7.8% had diabetes. During a median follow-up period of 32 months, 197 MACE occurred. In men, the adjusted hazard ratio (HR) was 1.84 [95% confidence interval (CI), 1.35-2.49; P  < 0.001). The HR increased to 2.03 (95% CI, 1.89-2.17; P  < 0.001) with a cut-off value of 35 mmHg for a 10 mmHg increase in sleep-through morning surge. The increased adjusted HR associated with the morning rise persisted for each secondary endpoint, including 21 cardiovascular deaths [HR: 2.70 (95% CI, 2.03-3.60; P  < 0.001)], 78 myocardial infarctions [HR: 1.92 (95% CI, 1.72-2.15; P  < 0.001)], 24 hospitalisations for heart failure [HR: 1.77 (95% CI, 1.48-2.12; P  < 0.001)], 22 strokes [HR: 2.32 (95% CI, 1.85-2.91; P  < 0.001)], and 52 atrial fibrillations [HR: 1.94 (95% CI, 1.71-2.20; P  < 0.001)]., Conclusion: The morning BP rise was the most important circadian prognostic factor for MACE in patients with hypertension, which deserves more attention., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The signaling mechanism of the cardioprotective effect of deltorphin II was studied in models of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used the selective δ 2 -opioid receptor agonist deltorphin II (0.12 mg/kg), which was administered intravenously 5 min before reperfusion, the PI3K inhibitor wortmannin (0.025 mg/kg), the ERK1/2 blocker PD-098059 (0.5 mg/kg), the inhibitor JAK2 AG490 (3 mg/kg). All kinase blockers were administered 10 min before reperfusion. The infarct-limiting effect of deltorphin II is associated with the activation of PI3K and ERK1/2 and does not depend on JAK2., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

In male Wistar rats, coronary occlusion (45 min) and reperfusion (120 min) were modeled. Selective δ 2 -opioid receptor agonist (deltorphin II, 0.12 mg/kg) was administered intravenously 5 min before reperfusion; NO synthase inhibitor (L-NAME, 10 mg/kg), MPT pore blocker (atractyloside, 5 mg/kg), and protein kinase A inhibitor (H-89, 10 μg/kg) were administered intravenously 10 min before reperfusion. Deltorphin II administered before reperfusion led to a 2-fold decrease in the infarct size. The infarct-limiting effect of deltorphin II was associated with blockade of MPT pore. Protein kinase A and NO synthase were not involved in the cardioprotective effect of deltorphin II., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium-induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin-43 preservation. After stabilization in Krebs-Henseleit solution (4.5 mEq/L K + ), isolated hearts from Wistar rats underwent perfusion with low-potassium (1 mEq/L) solution and melatonin (100 μmol/L), a melatonin receptor blocker (luzindole, 5 μmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation. Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin-43 were examined. Melatonin reduced the incidence of low potassium-induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin-43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin-43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium-induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin-43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown., Objectives: To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension., Materials: Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 μM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion., Results: 1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test)., Conclusions: Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Light pollution is a global environmental issue that affects photosensitive organisms. For instance, several researchers have recognized melatonin suppression in humans as a direct cause of long-term exposure to high artificial light levels at night. Others have identified low melatonin levels as a risk factor for a higher prevalence of hormone-sensitive cancer. This paper analyzes the association between light pollution, estimated as the emission analysis of satellite worldwide nighttime light collections from 1999 to 2012, and 25,025 breast and 16,119 prostate cancer events from 2003 to 2012. Both types of cancer increased during the study period, but light pollution increased in urban and peri-urban areas and decreased in rural areas. Cumulative light pollution during 5 years showed a positive association with breast cancer but not with prostate cancer. The association between light pollution and breast cancer persisted when adjusted to age-standardized rates with a mean increase of 10.9 events per 100,000 population-year (95% confidence interval 7.0 to 14.8). We conclude that exposure to elevated light pollution levels could be a risk factor for breast cancer in Slovakia. This work can interest researchers who study relationships between atmospheric pollutants and the growing cancer epidemic. The results and the methodology can be extrapolated to any country in the world if data is available., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Postoperative atrial fibrillation (POAF) complicates 15% to 40% of cardiovascular surgeries. Its incidence progressively increases with aging, reaching 50% in octogenarians. This arrhythmia is usually transient but it increases the risk of embolic stroke, prolonged hospital stay, and cardiovascular mortality. Though many pathophysiological mechanisms are known, POAF prediction is still a hot topic of discussion. Doppler echocardiogram and, lately, strain echocardiography have shown significant capacity to predict POAF. Alterations in oxidative stress, calcium handling, mitochondrial dysfunction, inflammation, fibrosis, and tissue aging are among the mechanisms that predispose patients to the perfect "atrial storm". Manifestations of these mechanisms have been related to enlarged atria and impaired function, which can be detected prior to surgery. Specific alterations in the atrial reservoir and pump function, as well as atrial dyssynchrony determined by echocardiographic atrial strain, can predict POAF and help to shed light on which patients could benefit from preventive therapy.

Aging comes with gradual loss of functions that increase the vulnerability to disease, senescence, and death. The mechanisms underlying these processes are linked to a prolonged imbalance between damage and repair. Damaging mechanisms include oxidative stress, mitochondrial dysfunction, chronodisruption, inflammation, and telomere attrition, as well as genetic and epigenetic alterations. Several endogenous tissue repairing mechanisms also decrease. These alterations associated with aging affect the entire organism. The most devastating manifestations involve the cardiovascular system and may lead to lethal cardiac arrhythmias. Together with structural remodeling, electrophysiological and intercellular communication alterations during aging predispose to arrhythmic events. Despite the knowledge on repairing mechanisms in the cardiovascular system, effective antiaging strategies able to reduce the risk of arrhythmias are still missing. Melatonin is a promising therapeutic candidate due to its pleiotropic actions. This indoleamine regulates chronobiology and endocrine physiology. Of relevance, melatonin is an antiaging, antioxidant, antiapoptotic, antiarrhythmic, immunomodulatory, and antiproliferative molecule. This review focuses on the protective effects of melatonin on age-induced cardiac functional and structural alterations, potentially becoming a new fountain of youth for the heart., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Margarita Segovia-Roldan et al.)

Aging leads to structural and electrophysiological changes that increase the risk of postoperative atrial arrhythmias; however, noninvasive preoperative markers of atrial proarrhythmic conditions are still needed. This study is aimed at assessing whether interatrial dyssynchrony determined using two-dimensional speckle tracking echocardiography relates to proarrhythmic structural and functional remodeling. A cohort of 45 patients in sinus rhythm referred for cardiac surgery was evaluated by echocardiography and surface electrocardiogram the day before the intervention. Transmembrane potential, connexin, and potassium channel distribution, inflammatory, and nitrooxidative markers were measured from right atrial tissue obtained from patients. A difference greater than 40 milliseconds between right and left atrial free wall contraction confirmed the presence of interatrial dyssynchrony in 21 patients. No difference in relation with age, previous diseases, and 2-dimensional echocardiographic findings as well as average values of global longitudinal right and left atrial strain were found between synchronic and dyssynchronic patients. Postoperative atrial fibrillation incidence increased from 8.3% in the synchronic group to 33.3% in the dyssynchronic ones. P wave duration showed no difference between groups. Action potentials from dyssynchronous patients decreased in amplitude, maximal rate of depolarization, and hyperpolarized. Duration at 30% of repolarization increased, being markedly shorter at 90% of repolarization. Only the dyssynchronous group showed early and delayed afterdepolarizations. Atrial tissue of dyssynchronous patients displayed lateralization of connexin 40 and increased connexin 43 expression and accumulation of tumor necrosis factor- α in the intercalated disc. Tumor necrosis factor- α did not colocalize, however, with lateralized connexin 40. Nitroxidative marks and K ATP channels increased perivascularly and in myocytes. Our results demonstrate that, as compared to a traditional surface electrocardiogram, the novel noninvasive echocardiographic evaluation of interatrial dyssynchrony provides a better identification of nonaged-related proarrhythmic atrial remodeling with increased susceptibility to postoperative atrial fibrillation., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Francisco J. Sánchez et al.)

Cardiac connexin-43 (Cx43) creates gap junction channels (GJCs) at intercellular contacts and hemi-channels (HCs) at the peri-junctional plasma membrane and sarcolemmal caveolae/rafts compartments. GJCs are fundamental for the direct cardiac cell-to-cell transmission of electrical and molecular signals which ensures synchronous myocardial contraction. The HCs and structurally similar pannexin1 (Panx1) channels are active in stressful conditions. These channels are essential for paracrine and autocrine communication through the release of ions and signaling molecules to the extracellular environment, or for uptake from it. The HCs and Panx1 channel-opening profoundly affects intracellular ionic homeostasis and redox status and facilitates via purinergic signaling pro-inflammatory and pro-fibrotic processes. These conditions promote cardiac arrhythmogenesis due to the impairment of the GJCs and selective ion channel function. Crosstalk between GJCs and HCs/Panx1 channels could be crucial in the development of arrhythmogenic substrates, including fibrosis. Despite the knowledge gap in the regulation of these channels, current evidence indicates that HCs and Panx1 channel activation can enhance the risk of cardiac arrhythmias. It is extremely challenging to target HCs and Panx1 channels by inhibitory agents to hamper development of cardiac rhythm disorders. Progress in this field may contribute to novel therapeutic approaches for patients prone to develop atrial or ventricular fibrillation.

Pharmacological concentrations of melatonin reduce reperfusion arrhythmias, but less is known about the antiarrhythmic protection of the physiological circadian rhythm of melatonin. Bilateral surgical removal of the superior cervical ganglia irreversibly suppresses melatonin rhythmicity. This study aimed to analyze the cardiac electrophysiological effects of the loss of melatonin circadian oscillation and the role played by myocardial melatonin membrane receptors, SERCA 2A , TNFα, nitrotyrosine, TGFβ, K ATP channels, and connexin 43. Three weeks after bilateral removal of the superior cervical ganglia or sham surgery, the hearts were isolated and submitted to ten minutes of regional ischemia followed by ten minutes of reperfusion. Arrhythmias, mainly ventricular tachycardia, increased during reperfusion in the ganglionectomy group. These hearts also suffered an epicardial electrical activation delay that increased during ischemia, action potential alternants, triggered activity, and dispersion of action potential duration. Hearts from ganglionectomized rats showed a reduction of the cardioprotective MT 2 receptors, the MT 1 receptors, and SERCA 2A . Markers of nitroxidative stress (nitrotyrosine), inflammation (TNFα), and fibrosis (TGFβ and vimentin) did not change between groups. Connexin 43 lateralization and the pore-forming subunit (Kir6.1) of K ATP channels increased in the experimental group. We conclude that the loss of the circadian rhythm of melatonin predisposes the heart to suffer cardiac arrhythmias, mainly ventricular tachycardia, due to conduction disorders and changes in repolarization.

Melatonin is assumed to confer cardioprotective action via antioxidative properties. We evaluated the association between ventricular tachycardia and/or ventricular fibrillation (VT/VF) incidence, oxidative stress, and myocardial electrophysiological parameters in experimental ischemia/reperfusion under melatonin treatment. Melatonin was given to 28 rats (10 mg/kg/day, orally, for 7 days) and 13 animals received placebo. In the anesthetized animals, coronary occlusion was induced for 5 min followed by reperfusion with recording of unipolar electrograms from ventricular epicardium with a 64-lead array. Effects of melatonin on transmembrane potentials were studied in ventricular preparations of 7 rats in normal and "ischemic" conditions. Melatonin treatment was associated with lower VT/VF incidence at reperfusion, shorter baseline activation times (ATs), and activation-repolarization intervals and more complete recovery of repolarization times (RTs) at reperfusion (less baseline-reperfusion difference, ΔRT) ( p < 0.05). Superoxide dismutase (SOD) activity was higher in the treated animals and associated with ΔRT ( p = 0.001), whereas VT/VF incidence was associated with baseline ATs ( p = 0.020). In vitro, melatonin led to a more complete restoration of action potential durations and resting membrane potentials at reoxygenation ( p < 0.05). Thus, the antioxidative properties of melatonin were associated with its influence on repolarization duration, whereas the melatonin-related antiarrhythmic effect was associated with its oxidative stress-independent action on ventricular activation.

Ischemic postconditioning (IPoC) reduces reperfusion arrhythmias but the antiarrhythmic mechanisms remain unknown. The aim of this study was to analyze IPoC electrophysiological effects and the role played by adenosine A 1 , A 2A and A 3 receptors, protein kinase C, ATP-dependent potassium (K ATP ) channels, and connexin 43. IPoC reduced reperfusion arrhythmias (mainly sustained ventricular fibrillation) in isolated rat hearts, an effect associated with a transient delay in epicardial electrical activation, and with action potential shortening. Electrical impedance measurements and Lucifer-Yellow diffusion assays agreed with such activation delay. However, this delay persisted during IPoC in isolated mouse hearts in which connexin 43 was replaced by connexin 32 and in mice with conditional deletion of connexin 43. Adenosine A 1 , A 2A and A 3 receptor blockade antagonized the antiarrhythmic effect of IPoC and the associated action potential shortening, whereas exogenous adenosine reduced reperfusion arrhythmias and shortened action potential duration. Protein kinase C inhibition by chelerythrine abolished the protective effect of IPoC but did not modify the effects on action potential duration. On the other hand, glibenclamide, a K ATP inhibitor, antagonized the action potential shortening but did not interfere with the antiarrhythmic effect. The antiarrhythmic mechanisms of IPoC involve adenosine receptor activation and are associated with action potential shortening. However, this action potential shortening is not essential for protection, as it persisted during protein kinase C inhibition, a maneuver that abolished IPoC protection. Furthermore, glibenclamide induced the opposite effects. In addition, IPoC delays electrical activation and electrical impedance recovery during reperfusion, but these effects are independent of connexin 43.

Lethal ventricular arrhythmias increase in patients with chronic kidney disease that suffer an acute coronary event. Chronic kidney disease induces myocardial remodeling, oxidative stress, and arrhythmogenesis. A manifestation of the relationship between kidney and heart is the concomitant reduction in vitamin D receptor (VDR) and the increase in angiotensin II receptor type 1 (AT 1 ). Melatonin has renal and cardiac protective actions. One potential mechanism is the increase in the heat shock protein 70 (Hsp70)-an antioxidant factor. We aim to determine the mechanisms involved in melatonin (Mel) prevention of kidney damage and arrhythmogenic heart remodeling. Unilateral ureteral-obstruction (UUO) and sham-operated rats were treated with either melatonin (4 mg/kg/day) or vehicle for 15 days. Hearts and kidneys from obstructed rats showed a reduction in VDR and Hsp70. Associated with AT 1 up-regulation in the kidneys and the heart of UUO rats also increased oxidative stress, fibrosis, apoptosis, mitochondrial edema, and dilated crests. Melatonin prevented these changes and ventricular fibrillation during reperfusion. The action potential lengthened and hyperpolarized in melatonin-treated rats throughout the experiment. We conclude that melatonin prevents renal damage and arrhythmogenic myocardial remodeling during unilateral ureteral obstruction due to a decrease in oxidative stress/fibrosis/apoptosis associated with AT 1 reduction and Hsp70-VDR increase., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: Here, we review the known relations between hypertension and obesity to inflammation and postulate the endogenous protective effect of melatonin and its potential as a therapeutic agent. We will describe the multiple effects of melatonin on blood pressure, adiposity, body weight, and focus on mitochondrial-related anti-inflammatory and antioxidant protective effects., Recent Findings: Hypertension and obesity are usually associated with systemic and tissular inflammation. The progressive affection of target-organs involves multiple mediators of inflammation, most of them redundant, which make anti-inflammatory strategies ineffective. Melatonin reduces blood pressure, body weight, and inflammation. The mechanisms of action of this ancient molecule of protection involve multiple levels of action, from subcellular to intercellular. Mitochondria is a key inflammatory element in vascular and adipose tissue and a potential pharmacological target. Melatonin protects against mitochondrial dysfunction. Melatonin reduces blood pressure and adipose tissue dysfunction by multiple anti-inflammatory/antioxidant actions and provides potent protection against mitochondria-mediated injury in hypertension and obesity. This inexpensive and multitarget molecule has great therapeutic potential against both epidemic diseases.

Metabolic syndrome (MetS) is a risk factor for sudden cardiac death in humans, but animal models are needed for the study of this association. Grape pomace (GP), obtained from the winemaking process, contains phenolic compounds with potential cardioprotective effects. The aim of this study was to evaluate if a high-fat-fructose (HFF) diet facilitates the occurrence of arrhythmias during the reperfusion, and if a GP supplementation could counteract these effects. Wistar rats were fed with control (Ctrl), HFF diet and HFF plus GP (1 g kg -1 day -1 ) for six weeks. The HFF diet induces characteristic features of MetS (higher systolic blood pressure, dyslipidemia and insulin resistance) which was attenuated by GP supplementation. In addition, HFF induced increased reperfusion arrhythmias that were reduced upon GP supplementation. GP also reduced the non-phosphorylated form of connexin-43 (Cx43) while enhancing heart p-AKT and p-eNOS protein levels and reducing Nox4 levels enhanced by the HFF diet, indicating that GP may increase NO bioavailability in the heart. We found a murine model of MetS with increased arrhythmogenesis and translational value. Furthermore, GP prevents diet-induced heart dysfunction and metabolic alterations. These results highlight the potential utilization of winemaking by-products containing significant amounts of bioactive compounds to prevent/attenuate MetS-associated cardiovascular pathologies.

Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia-reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials., (© The Author(s) 2014.)

Melatonin reduces reperfusion arrhythmias when administered before coronary occlusion, but in the clinical context of acute coronary syndromes, most of the therapies are administered at the time of reperfusion. Patients frequently have physiological modifications that can reduce the response to therapeutic interventions. This work determined whether acute melatonin administration starting at the moment of reperfusion protects against ventricular arrhythmias in Langendorff-perfused hearts isolated from fructose-fed rats (FFR), a dietary model of metabolic syndrome, and from spontaneous hypertensive rats (SHR). In both experimental models, we confirmed metabolic alterations, a reduction in myocardial total antioxidant capacity and an increase in arterial pressure and NADPH oxidase activity, and in FFR, we also found a decrease in eNOS activity. Melatonin (50 μm) initiated at reperfusion after 15-min regional ischemia reduced the incidence of ventricular fibrillation from 83% to 33% for the WKY strain, from 92% to 25% in FFR, and from 100% to 33% in SHR (P = 0.0361, P = 0.0028, P = 0.0013, respectively, by Fisher's exact test, n = 12 each). Although, ventricular tachycardia incidence was high at the beginning of reperfusion, the severity of the arrhythmias progressively declined in melatonin-treated hearts. Melatonin induced a shortening of the action potential duration at the beginning of reperfusion and in the SHR group also a faster recovery of action potential amplitude. We conclude that melatonin protects against ventricular fibrillation when administered at reperfusion, and these effects are maintained in hearts from rats exposed to major cardiovascular risk factors. These results further support the ongoing translation to clinical trials of this agent., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Reperfusion arrhythmias are currently attributed to ionic imbalance and oxidative stress. Tamoxifen is a potent antioxidant that also modulates some ionic transport pathways. In this work, we tried to correlate the electrophysiological effects of 1, 2, and 5 µM of tamoxifen with the incidence and severity of arrhythmias appearing on reperfusion after 10 minutes of coronary occlusion in isolated hearts from female rats. All tamoxifen concentrations inhibited the action potential shortening observed in the control hearts during late ischemia (6-10 minutes), whereas 2 and 5 µM also reduced the resting membrane potential depolarization. The incidence of sustained ventricular tachycardia and/or ventricular fibrillation on reperfusion decreased from 10 of 12 (control group) to 5 of 10 (1 µM, P = 0.1718), 4 of 12 (2 µM, P = 0.0361), and 2 of 10 (5 µM, P = 0.0083). The possible role of chloride currents activated by cell swelling in these effects was explored in hearts submitted to a 10-minute hypotonic challenge, where tamoxifen (5 µM) blocked the action potential shortening and the late resting membrane potential depolarization produced by hypotonicity, mimicking its action in late ischemia. Tamoxifen produced a similar increase of the total antioxidant capacity of myocardial samples at all the concentration tested. In conclusion, our data strongly suggest that the antiarrhythmic action of this agent is mediated by its electrophysiological effect derived from modulation of chloride currents activated by cell swelling.

The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n = 8 each): control (W); W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR): WKY rats receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR): SHR receiving 10% (w/v) fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases), VCAM-1, and NF- κ B by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.

Aim: This study tests the hypothesis postulating that metabolic syndrome induced by chronic administration of fructose to spontaneously hypertensive rats (FFHR) generates impairment in vascular repair by endothelial progenitor cells (EPC)., Materials and Methods: TO CHARACTERIZE THE VASCULAR ADVERSE ENVIRONMENT PRESENT IN THIS EXPERIMENTAL MODEL WE MEASURED: NAD(P)H oxidase activity, eNOS activity, presence of apoptosis in the arterial wall, all these parameters were most affected in the FFHR group. Also, we found decreased level and proliferative capacity of EPC measured by flow cytometry and colonies forming units assay in cultured cells, respectively, in both groups treated with fructose; FFHR (SHR fructose fed rats) and FFR (WKY fructose fed rats) compared with their controls; SHR and WKY., Results: The fructose-fed groups FFR and SHR also showed an incremented number of apoptotic (annexinV+/7AADdim) EPC measured by flow cytometry that returns to almost normal values after eliminating fructose administration., Conclusion: Our findings suggest that increased apoptosis levels of EPC generated in this experimental model could bein part the underlying cause for the impaired vascular repair by in EPC.

Background: Imbalance in adipocytokines secretion is related to the development of metabolic syndrome (MS). In addition, moderate consumption of red wine (RW) decreases the risk of cardiovascular disease. The aim of this study was to evaluate the effects of moderate consumption of RW or ethanol (E) on adiponectin and resistin expression, and vascular alterations in fructose-fed rats (FFRs) as an experimental model of MS., Methods: Thirty-day-old male Wistar rats were assigned to control (C), F (10% fructose in drinking water), F+E (4.5 ml/kg), and F+RW (35 ml/kg of Malbec RW containing 4.5 ml/kg E). E and RW were administered during the last 4 weeks of a 10-week period., Results: RW administration to F rats was able to significantly decrease insulin resistance, mesenteric adipose tissue weight, and systolic blood pressure (SBP) compared to F group. F+E only reduced the SBP (P < 0.05 vs. F). F+RW also reduced aortic NAD(P)H-oxidase activity, NAD(P)H subunits Nox4 expression in mesenteric tissue, plasma thiobarbituric acid reactive substances (TBARS), and recovered plasma total antioxidant activity (TAA) compared to F and F+E groups (P < 0.05). Adiponectin expression decreased, whereas resistin, vascular cell adhesion molecules-1 (VCAM-1), and nuclear factor-κB (NF-κB) expression and vascular remodeling in mesenteric arteries were higher in F than in C group (P < 0.05). Only RW was able to partially reverse the aforementioned alterations., Conclusion: In this study, Malbec RW, but not alcohol alone, improved the balance of adipocytokines and attenuated the oxidative stress and vascular inflammation in a model of MS, suggesting that nonalcohol components of RW are responsible for the beneficial effects.

The present study examines the effect of chronic administration of dealcoholized red wine Malbec (DRW) on vascular remodeling and NAD(P)H oxidase and endothelial nitric oxide synthase activity (eNOS) in an experimental model of metabolic syndrome induced by fructose administration. Thirty-day old male Wistar rats were fed a normal rat diet (control) or the same diet plus 10% fructose in drinking water (FFR). During the last 4 weeks of a 10-week period of the corresponding diet, a subgroup of control and FFR (n=8 each) received DRW in their drinking water. Systolic blood pressure (SBP), a homeostasis model assessment of insulin resistance (HOMA-IR), aortic NAD(P)H oxidase and eNOS activity in the heart and vascular tissue were evaluated. Vascular remodeling was evaluated in the left carotid artery (CA) and interlobar, arcuate and interlobular renal arteries (RA) through lumen to media (L/M) ratio determination. At the end of the study FFR increased the SBP (p < 0.001), HOMA-IR (p < 0.001), and aortic NAD(P)H oxidase activity (p < 0,05) but reduced cardiac and vascular eNOS activity (p < 0.01), L/M ratio in CA (p < 0.001) and RA (p < 0.01) compared with the C group. DRW reduced SBP (p < 0.05), aortic NAD(P)H oxidase (p < 0.05), and recovered eNOS activity (p < 0.001) and L/M in CA (p < 0.001) and RA (p < 0.001) compared with FFR. This study provides new data about the beneficial effect of DRW on oxidative stress and vascular remodeling in the experimental model of metabolic syndrome. Data suggest the participation of mechanisms involving oxidative stress in FFR alterations and the usefulness of natural antioxidant substances present in red wine in the reversion of these changes., (This journal is © The Royal Society of Chemistry 2010)

Reperfusion after a short period of cardiac ischemia triggers ventricular arrhythmias attributable to ionic imbalance and oxidative stress. Melatonin offers some degree of protection, but its effects on the cardiac action potentials are unknown. We evaluated the effects of 5, 10, 20 and 50 microM melatonin in isolated perfused rat hearts subjected to 10 min of regional ischemia. ECG and membrane potentials were synchronously displayed. After 15 min of reperfusion, total antioxidant capacity (TAC) was determined. Melatonin did not change the ischemic depolarization nor the action potential amplitude depression, but at the end of ischemia the action potential duration (APD) decreased in control and 5 microM melatonin-treated hearts. By contrast, it returned to preischemic levels in hearts given 20 and 50 microM melatonin. Melatonin reduced the incidence of reperfusion arrhythmias from 100% in control to 50% in 5 and 10 microM, to 40% in 20 microM and 30% in 50 microM hearts. TAC values were higher at all melatonin concentrations. We conclude that melatonin reduced the incidence of reperfusion arrhythmias because of its antioxidant effects. In addition, at 20 and 50 microM lengthened APD and promoted an improved protection. This latter effect should be considered when in vivo applications of melatonin are considered.

Despite the early recognition of obesity as an epidemic with global implications, research on its pathogenesis and therapeutic approach is still on the rise. The literature of the 21st century records an excess weight found in up to 1/3 of children. Both the determining factors and its systemic effects are multiple and variable. Regarding its involvement in the potentiation of cardio-vascular, pulmonary, digestive, metabolic, neuro-psychic or even dermatological diseases, the information is already broadly outlined. The connection between the underlying disease and the associated comorbidities seems to be partially attributable to oxidative stress. In addition to these, and in the light of the recent COVID-19 pandemic, the role played by oxidative stress in the induction, maintenance and potentiation of chronic inflammation among overweight children and adolescents becomes a topic of interest again. Thus, this review's purpose is to update general data on obesity, with an emphasis on the physiopathological mechanisms that underlie it and involve oxidative stress. At the same time, we briefly present the latest principles of pathology diagnosis and management. Among these, we will mainly emphasize the impact played by endogenous and exogenous antioxidants in the evolutionary course of pediatric obesity. In order to achieve our objectives, we will refer to the most recent studies published in the specialized literature. [ABSTRACT FROM AUTHOR]

Melatonin has been proven to have antiarrhythmic potential; however, several studies have recently challenged this view. Herein, using a mouse model of obesity-induced atrial fibrillation (AF), we tentatively explored whether exogenous melatonin supplementation could increase AF susceptibility in the context of obesity. We observed that an 8-week drinking administration of melatonin (60 µg/ml in water) induced a greater susceptibility to AF in obese mice, although obesity-induced structural remodeling was alleviated. An investigation of systemic insulin sensitivity showed that melatonin treatment improved insulin sensitivity in obese mice, whereas it inhibited glucose-stimulated insulin secretion. Notably, melatonin treatment inhibited protein kinase B (Akt) signaling in the atria of obese mice and palmitate-treated neonatal rat cardiomyocytes, thereby providing an AF substrate. Melatonin increased lipid stress in obesity, as evidenced by elevated lipid accumulation and lipolysis-related gene expression, thus contributing to the impairment in atrial Akt signaling. Taken together, our results demonstrated that melatonin could increase AF susceptibility in obesity, probably due to increased lipid stress and resultant impairment of atrial Akt signaling. Our findings suggest that special precautions should be taken when administering melatonin to obese subjects., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Islamic instructions suggest waking up near dawn and praying to Allah. This is the time of maximum melatonin secretion, a hormone whose main function is regulating the circadian rhythm. Melatonin secretion declines with age, leading to different clinical consequences. This study investigated the melatonin levels among night vigil prayers, non-prayer late sleepers, and those with regular night sleep. Methods: A questionnaire including information about age, gender, education, and occupation was used to collect the demographic information of the participants. Melatonin was measured with two blood draws (23:00 to 24:00 and 9:00 to 10:00). Results: There was a significant difference between the night vigil prayers’ nocturnal and daily melatonin and the melatonin levels of the other two groups. There was no significant difference in the average daily serum melatonin levels between regular night sleepers and non-praying late sleepers (P=0.306). Moreover, a significant negative relationship was found between age and nocturnal melatonin (r=0.38, P<0.0001) and between age and daily melatonin (r=0.25, P=0.02). Conclusion: Night vigil prayers had higher average nocturnal and daily serum melatonin levels than non-praying late sleepers and regular sleepers. Therefore, waking up at night accompanied by approaching Allah, prayer, supplication, and positive thoughts was related to release in melatonin. [ABSTRACT FROM AUTHOR]

In recent years, obesity has become one of the major diseases that affect human health and consume human health resources, especially when it causes comorbidities such as hypertension, diabetes, cardiovascular disease and kidney disease. Many studies have demonstrated that obesity is associated with the development of chronic kidney disease and can exacerbate the progression of end-stage renal disease. This review described the mechanisms associated with the development of obesity-associated nephropathy and the current relevant therapeutic modalities, with the aim of finding new therapeutic targets for obesity-associated nephropathy. The mechanisms of obesity-induced renal injury include, in addition to the traditional alterations in renal hemodynamics, the involvement of various mechanisms such as macrophage infiltration in adipose tissue, alterations in adipokines (leptin and adiponectin), and ectopic deposition of lipids. At present, there is no "point-to-point" treatment for obesity-induced kidney injury. The renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporter 2 (SGLT-2) inhibitors and bariatric surgery described in this review can reduce urinary protein to varying degrees and delay the progression of kidney disease. In addition, recent studies on the therapeutic effects of intestinal flora on obesity may reduce the incidence of obesity-related kidney disease from the perspective of primary prevention. Both of these interventions have their own advantages and disadvantages, so the continuous search for the mechanism of obesity-induced related kidney disease will be extremely helpful for the future treatment of obesity-related kidney disease. [ABSTRACT FROM AUTHOR]

The effect of preventive administration of melatonin on the arrhythmogenic substrate in the myocardium was studied in the rabbit model of acute ischemia/reperfusion in vivo. The animals treated with melatonin 60 min before ischemia induction had shorter median activation time compared to the control group (p=0.039), less pronounced shortening of repolarization durations in the ischemic zone during coronary occlusion (p=0.008), and more complete recovery of repolarization during reperfusion (p=0.027). In the melatonin group, the dispersion of repolarization was less than in the control group during both ischemic period (p=0.043) and reperfusion (p=0.038). Thus, preventive administration of melatonin mitigated the arrhythmogenic substrate in the heart under conditions of ischemia/reperfusion. [ABSTRACT FROM AUTHOR]

Melatonin treatment was reported to reduce the risk of cardiac arrhythmias, and crucial for this antiarrhythmic action was the effect of melatonin on activation spread. The aim of the present study was evaluation of the mechanisms of this activation enhancement. Experiments were performed in a total of 123 control and melatonin-treated (10 mg/kg, daily, for 7 days) male Wistar rats. In epicardial mapping studies (64 leads, interlead distance 0.5 mm) in the anesthetized animals, activation times (ATs) were determined in each lead as dV/dt minimum during QRS complex under sinus rhythm. Epicardial pacing was performed to measure conduction velocity (CV) across the mapped area. Average left ventricular ATs were shorter in the treated animals as compared to the controls, whereas the minimal epicardial ATs indicating the duration of activation propagation via the ventricular conduction system did not differ between the groups. CV was higher in the treated groups indicating that melatonin affected conduction via contractile myocardium The area of Cx43-derived fluorescence, as well as the expression of Cx43 protein, was similar in ventricles in the control and melatonin-treated groups. Expression of Gja1 gene transcripts encoding Cx43, was increased in the last group. An uncoupling agent octanol modified myocardial conduction properties (time of activation, action potential upstroke velocity, passive electrotonic phase duration) similarly in both groups. On the other hand, the expression of both Scn5a gene transcripts encoding Nav1.5 proteins, as well as peak density of transmembrane sodium current were increased in the ventricular myocytes from the melatonin-treated animals. Thus, a week-long melatonin treatment caused the increase of conduction velocity via enhancement of sodium channel proteins expression and increase of sodium current in the ventricular myocytes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cardiovascular diseases (CVDs) are the leading global cause of mortality and disability, tending to happen in younger individuals in developed countries. Despite improvements in medical treatments, the therapy and long-term prognosis of CVDs such as myocardial ischemia-reperfusion, atherosclerosis, heart failure, cardiac hypertrophy and remodeling, cardiomyopathy, coronary artery disease, myocardial infarction, and other CVDs threatening human life are not satisfactory enough. Therefore, many researchers are attempting to identify novel potential therapeutic methods for the treatment of CVDs. Melatonin is an anti-inflammatory and antioxidant agent with a wide range of therapeutic properties. Recently, several investigations have been carried out to evaluate its effectiveness and efficiency in CVDs therapy, focusing on mechanistic pathways. Herein, this review aims to summarize current findings of melatonin treatment for CVDs., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Artificial light at night (ALAN) is rapidly growing and expanding globally, posing threats to ecological safety. Urban light pollution prevention and control are moving toward urban artificial light ecology construction. To clarify the need for light ecology construction, this work analyzes 1690 articles on ALAN and light pollution and 604 on ecological light pollution from 1998 to 2022. The development process and thematic evolution of light pollution research are combed through, the historical inevitability of artificial light ecology construction is excavated, and the ecological risks of light pollution to typical animals are summarized. The results show that international research has advanced to the ecological risk factors of light pollution and the related stress mechanisms, the quantification, prediction, and pre-warning by multiple technical means, and the translation of light pollution research outcomes to prevention and control practices. While Chinese scholars have begun to pay attention to the ecological risks of light pollution, the evaluation indicators and prevention and control measures remain primarily based on human-centered needs. Therefore, a more integrated demand-side framework of light ecology construction that comprehensively considers multiple risk receptors is further constructed. Given the development trend in China, we clarified the consistency of the ecological effect of landscape lighting with landsense ecology and the consistency of light ecological risk prevention and control with the concept of One Health. Ultimately, landsense light ecology is proposed based on the "One Health" concept. This work is expected to provide a reference and inspiration for future construction of urban artificial light ecology. [ABSTRACT FROM AUTHOR]

Melatonin (MLT) is crucial in controlling human sleep-wake patterns. While it has long been recognized for regulating circadian rhythms, its demonstrated efficacy in managing various diseases has recently gained considerable attention. This review discusses MLT's potential preventative and therapeutic effects on various diseases. Several studies have focused on examining the molecular mechanisms through which MLT brings about its protective or therapeutic effects on various diseases, including cancer, obesity, coronavirus, and cardiovascular diseases. Numerous preventative and therapeutic applications of MLT have been proposed, resulting from its ability to function as an antioxidant, anti-cancer, anti-inflammatory, and immune-regulating agent. There is a need for further research to determine MLT's long-term effects on antioxidant defense systems, its preventative and therapeutic benefits, and its molecular basis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Succinate accumulates during myocardial ischemia and is rapidly oxidized during reperfusion, leading to reactive oxygen species (ROS) production through reverse electron transfer (RET) from mitochondrial complex II to complex I, and favoring cell death. Given that connexin 43 (Cx43) modulates mitochondrial ROS production, we investigated whether Cx43 influences RET using inducible knock-out Cx43 Cre-ER(T)/fl mice. Oxygen consumption, ROS production, membrane potential and coenzyme Q (CoQ) pool were analyzed in subsarcolemmal (SSM, expressing Cx43) and interfibrillar (IFM) cardiac mitochondria isolated from wild-type Cx43 fl/fl mice and Cx43 Cre-ER(T)/fl knock-out animals treated with 4-hydroxytamoxifen (4OHT). In addition, infarct size was assessed in isolated hearts from these animals submitted to ischemia-reperfusion (IR), and treated or not with malonate, a complex II inhibitor attenuating RET. Succinate-dependent ROS production and RET were significantly lower in SSM, but not IFM, from Cx43-deficient animals. Mitochondrial membrane potential, a RET driver, was similar between groups, whereas CoQ pool (2.165 ± 0.338 vs. 4.18 ± 0.55 nmol/mg protein, p < 0.05) and its reduction state were significantly lower in Cx43-deficient animals. Isolated hearts from Cx43 Cre-ER(T)/fl mice treated with 4OHT had a smaller infarct size after IR compared to Cx43 fl/fl , despite similar concentration of succinate at the end of ischemia, and no additional protection by malonate. Cx43 deficiency attenuates ROS production by RET in SSM, but not IFM, and was associated with a decrease in CoQ levels and a change in its redox state. These results may partially explain the reduced infarct size observed in these animals and their lack of protection by malonate., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Cardiovascular diseases (CVDs) are the leading causes of death and illness worldwide. While there have been advancements in the treatment of CVDs using medication and medical procedures, these conventional methods have limited effectiveness in halting the progression of heart diseases to complete heart failure. However, in recent years, the hormone melatonin has shown promise as a protective agent for the heart. Melatonin, which is secreted by the pineal gland and regulates our sleep-wake cycle, plays a role in various biological processes including oxidative stress, mitochondrial function, and cell death. The Sirtuin (Sirt) family of proteins has gained attention for their involvement in many cellular functions related to heart health. It has been well established that melatonin activates the Sirt signaling pathways, leading to several beneficial effects on the heart. These include preserving mitochondrial function, reducing oxidative stress, decreasing inflammation, preventing cell death, and regulating autophagy in cardiac cells. Therefore, melatonin could play crucial roles in ameliorating various cardiovascular pathologies, such as sepsis, drug toxicity-induced myocardial injury, myocardial ischemia-reperfusion injury, hypertension, heart failure, and diabetic cardiomyopathy. These effects may be partly attributed to the modulation of different Sirt family members by melatonin. This review summarizes the existing body of literature highlighting the cardioprotective effects of melatonin, specifically the ones including modulation of Sirt signaling pathways. Also, we discuss the potential use of melatonin-Sirt interactions as a forthcoming therapeutic target for managing and preventing CVDs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Moreover, it is mentioned as one of the important causes of death due to heart disease, which imposes an undeniable financial burden on public health systems. Almost 1 out of 4 individuals aged 40 to 55 will experience AF at some point during their life. Increasing the pressure or the volume of the atria over time leads to the activation of fibroblasts, resulting in the accumulation of extracellular matrix and fibrosis. By disturbing electrical conduction, fibrosis creates microreentrant circuits, which can develop into AF. In this article, we evaluated the vital role of interleukins and inflammatory mediators in the pathogenesis, prognosis, and treatment of AF. We also discussed the importance of the broader use of interleukins in the clinical management of AF patients. Interleukins and inflammatory markers can be used as markers of diagnosis, cardiovascular events, and mortality in AF patients. Finally, the utilization of substances upregulating IL-10, such as resolvin D1 (RvD1), or applying IL-6 down-regulators and inhibitors, including anti-IL-6 antibodies, colchicine, and C1q/tumor necrosis factor-related protein-9 (CTRP9), are effective in the reduction of atrial interstitial fibrosis and treating AF patients. Interleukins are mediators of the immune system, which play vital roles, directly or indirectly, in many immune responses and have a wide range of effects on the systems in the body. Similarly, these interleukins can have versatile roles in igniting or attenuating cardiovascular disorders. However, due to the complexity and variability of their effects on the cardiovascular system, research is still ongoing to capture a complete and realistic image of the role of interleukins in the development of cardiovascular disorders. Atrial fibrillation occurs following the irregular rhythm of the beat in the atria. Subsequently, the normal blood flow from the atria to the ventricles will be disturbed. Atrial fibrillation is the most common heart arrhythmia that might need medical care. However, the probability of severe atrial fibrillation outcomes or symptoms is higher in people with underlying comorbidities. This review investigates the role of interleukins in the occurrence of atrial fibrillation and its long-term complications. Atrial fibrillation usually begins as occasional brief episodes that start and stop spontaneously, but it can progress to more persistent forms that are associated with an increased risk of stroke and heart failure.. Interleukins and inflammatory mediators can enhance atrial fibrillation by worsening the conductance of the electrical signal and by boosting the fibrogenesis and structural remodeling of the atria. Currently, based on the role of interleukins in atrial fibrillation, therapeutic methods are being developed to prevent and attenuate its serious consequences. These therapeutic methods can impressively affect and improve the lives of millions of people suffering from this disorder. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the effect and mechanism of action of adenosine 2 receptor (A2R) activation on myocardial ischemia reperfusion injury (MIRI) under diabetic conditions. Methods: MIRI type 2 diabetic rats and H9C2 cardiomyocytes were treated with A2R agonist and then subjected to hypoxia for 6 h and reoxygenation for 18 h. Myocardial damage, and infarct size were determined by cardiac ultrasound. Indicators of cardiomyocyte injury, creatine kinase-MB and cardiac troponin I were detected by Enzyme Linked Immunosorbent Assay. Endoplasmic reticulum stress (ERS) was determined through measuring the expression levels of ERS related genes GRP78, p-IRE1/IRE1, and p-JNKJNK. The mechanism of A2R cardio protection in MIRI through regulating ERS induced autophagy was determined by investigating the ER resident protein IRE-1. The ER-stress inducer Tunicamycin, and the IRE-1 inhibitor STF in combination with the A2R agonist NECA were used, and the cellular responses were assessed through autophagy proteins expression Beclin-1, p62, LC3 and apoptosis. Results: NECA improved left ventricular function post MIRI, limited myocardial infarct size, reduced myocardial damage, decreased cardiomyocytes apoptosis, and attenuated ERS induced autophagy through regulating the IRE-XBP1s-CHOP pathway. These actions resulted into overall protection of the myocardium against MIRI. Conclusion: In summary, A2R activation by NECA prior to ischemia attenuates apoptosis, reduces ERS induced autophagy and restores left ventricular function. This protective effect occurs through regulating the IRE1-XBPs-CHOP related mechanisms. NECA is thus a potential target for the treatment of MIRI in patient with type 2 diabetes. [ABSTRACT FROM AUTHOR]

In this study, we have screened genes involved in myocardial hypertrophy (MH) using a mice model for compensatory stress overload (transverse aortic constriction, TAC) and bioinformatics. Microarrays were downloaded, and according to the Venn diagram, three groups of data intersections were obtained. Gene function was analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), whereas protein-protein interactions (PPI) were analyzed using the STRING database. A mouse aortic arch ligation model was established to verify and screen the expression of hub genes. A total of 53 (DEGs) and 32 PPI genes were screened out. GO analysis showed DEGs mainly involved in cytokine and peptide inhibitor activity. KEGG analysis focused on ECM receptor interaction and osteoclast differentiation. Expedia co-expression gene network analysis showed that Serpina3n, Cdkn1a, Fos, Col5a2, Fn1 and Timp1 participated in the occurrence and development of MH. RT-qPCR verified that all the other 9 hub genes except Lox were highly expressed in TAC mice. This study lays a foundation for further study on the molecular mechanism of MH and for screening of molecular markers. [ABSTRACT FROM AUTHOR]

Hippocampal neuropathology is a recognized feature of the spontaneously hypertensive rat (SHR). The hippocampal alterations associate with cognitive impairment. We have shown that hippocampal abnormalities are reversed by 17β‐estradiol, a steroid binding to intracellular receptors (estrogen receptor α and β subtypes) or the membrane‐located G‐protein coupled estradiol receptor. Genistein (GEN) is a neuroprotective phytoestrogen which binds to estrogen receptor β and G‐protein coupled estradiol receptor. Here, we investigated whether GEN neuroprotection extends to SHR. For this purpose, we treated 5‐month‐old SHR for 2 weeks with 10 mg kg−1 daily s.c injections of GEN. We analyzed the expression of doublecortin+ neuronal progenitors, glial fibrillary acidic protein+ astrocytes and ionized calcium‐binding adapter molecule 1+ microglia in the CA1 region and dentate gyrus of the hippocampus using immunocytochemistry, whereas a quantitative real‐time polymerase chain reaction was used to measure the expression of pro‐ and anti‐inflammatory factors tumor necrosis factor α, cyclooxygenase‐2 and transforming growth factor β. We also evaluated hippocampal dependent memory using the novel object recognition test. The results showed a decreased number of doublecortin+ neural progenitors in the dentate gyrus of SHR that was reversed with GEN. The number of glial fibrillary acidic protein+ astrocytes in the dentate gyrus and CA1 was increased in SHR but significantly decreased by GEN treatment. Additionally, GEN shifted microglial morphology from the predominantly activated phenotype present in SHR, to the more surveillance phenotype found in normotensive rats. Furthermore, treatment with GEN decreased the mRNA of the pro‐inflammatory factors tumor necrosis factor α and cyclooxygenase‐2 and increased the mRNA of the anti‐inflammatory factor transforming growth factor β. Discrimination index in the novel object recognition test was decreased in SHR and treatment with GEN increased this parameter. Our results indicate important neuroprotective effects of GEN at the neurochemical and behavioral level in SHR. Our data open an interesting possibility for proposing this phytoestrogen as an alternative therapy in hypertensive encephalopathy. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review summarizes the involvement of inflammaging in vascular damage with focus on the epigenetic mechanisms by which inflammaging-induced hypertension is triggered. Recent Findings: Inflammaging in hypertension is a complex condition associated with the production of inflammatory mediators by the immune cells, enhancement of oxidative stress, and tissue remodeling in vascular smooth muscle cells and endothelial cells. Cellular processes are numerous, including inflammasome assembly and cell senescence which may involve mitochondrial dysfunction, autophagy, DNA damage response, dysbiosis, and many others. More recently, a series of noncoding RNAs, mainly microRNAs, have been described as possessing epigenetic actions on the regulation of inflammasome-related hypertension, emerging as a promising therapeutic strategy. Summary: Although there are a variety of pharmacological agents that effectively regulate inflammaging-related hypertension, a deeper understanding of the epigenetic events behind the control of vessel deterioration is needed for the treatment or even to prevent the disease onset. [ABSTRACT FROM AUTHOR]

Left ventricular hypertrophy (LVH) caused by high blood pressure is linked to increased mortality and arrhythmia risk. This study aimed to evaluate arrhythmia in hypertensive patients due to left ventricular hypertrophy (LVH). A cross-sectional study was performed, assessing participants' blood pressure, echocardiography and electrocardiography, and Holter monitoring in certain cases. There were 300 hypertensive patients >18 years attending the cardiology unit of Baghdad medical city. The study was conducted between January-June 2022. The electrocardiograms at rest for 300 adults with hypertension were investigated. 130 (43.5%) were females, and 170 (56.5%) were males. The mean age of participants was 58 years. Forty-nine (16.3%) patients had arrhythmia. As compared to those without arrhythmia, participants with arrhythmia were older (62.3 vs. 56.1, p=0.03), had a greater prevalence of left ventricular hypertrophy (24.5% vs. 12.7%, p=0.026), and more prone to experience cardiac failure (32.7% vs. 8.5%, p<0.011). Atrial fibrillation was found in 6 (27.2%) female patients and 5 (18.5%) males. In addition, two (7.4%) male patients and one female patient (4.5%) had atrial flutter, and premature ventricular contractions (PVCs) were noted in 10 (37%) and 11 (50%) patients. Left ventricular mass index (LVMI) was 103 gm/m2 in female patients and 119.2 gm/m2 in males. Palpitation was present in 22 (44.9%) female patients and 27 (55.1%) males. The study revealed that hypertensives with LVH have an arrhythmia frequency of 16.3%. The most common arrhythmias were atrial fibrillation and premature ventricular complex. [ABSTRACT FROM AUTHOR]

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Although acute melatonin treatment effectively reduces cardiac ischemia/reperfusion (I/R) injury in lean rats by modulating melatonin receptor 2 (MT2), there is no information regarding the temporal effects of melatonin administration during cardiac I/R injury in prediabetic obese rats. Prediabetic obese rats induced by chronic consumption of a high-fat diet (HFD) were used. The rats underwent a cardiac I/R surgical procedure (30-min of ischemia, followed by 120-min of reperfusion) and were randomly assigned to receive either vehicle or melatonin treatment. In the melatonin group, rats were divided into 3 different subgroups: (1) pretreatment, (2) treatment during ischemic period, (3) treatment at the reperfusion onset. In the pretreatment subgroup either a nonspecific MT blocker (Luzindole) or specific MT2 blocker (4-PPDOT) was also given to the rats prior to melatonin treatment. Pretreatment with melatonin (10 mg/kg) effectively reduced cardiac I/R injury by reducing infarct size, arrhythmia, and LV dysfunction. Reduction in impaired mitochondrial function, mitochondrial dynamic balance, oxidative stress, defective autophagy, and apoptosis were observed in rats pretreated with melatonin. Unfortunately, the cardioprotective benefits were not observed when 10-mg/kg of melatonin was acutely administered to the rats after cardiac ischemia. Thus, we increased the dose of melatonin to 20 mg/kg, and it was administered to the rats during ischemia or at the onset of reperfusion. The results showed that 20-mg/kg of melatonin effectively reduced cardiac I/R injury to a similar extent to the 10-mg/kg pretreatment regimen. The MT2 blocker inhibited the protective effects of melatonin. Acute melatonin treatment during cardiac I/R injury exerted protective effects in prediabetic obese rats. However, a higher dose of melatonin is required when given after the onset of cardiac ischemia. These effects of melatonin were mainly mediated through activation of MT2. [ABSTRACT FROM AUTHOR]

The iliac vein can be severely stenosed and occluded due to thrombosis, tumor compression, or an anatomical abnormality. Such occlusion could result in limb swelling, venous claudication, and persistent leg ulcers. Its devastating sequelae heavily impact patients lifestyles and the social economy. Due to a lack of a stable and easy-to-operate iliac vein occlusion (IVO) model, its underlying molecular mechanism and pathophysiological process has not been completely understood. Melatonin (MLT) plays a critical role in anti-inflammation, but the potential protective effect of melatonin on venous dysfunction induced by IVO has not been revealed. In this study, a mouse model of IVO was established to study the effects of MLT on injured veins. The results of laser speckle images and Evans blue showed that MLT inhibited venous permeability in an IVO mouse model. Furthermore, MLT suppressed inflammation of surrounding tissues close to the affected vein by inhibiting the mRNA levels of TNF-α, IL-1α, and MCP-1. In addition, endothelial injury was inhibited by MLT using zonula occludens protein-1 (ZO-1) staining. Taken together, we elucidated the therapeutic effect of MLT on vascular dysfunction induced by IVO, mainly by inhibiting the TNF-α, IL-1α, and MCP-1 mRNA levels, improving endothelial function, and inhibiting vascular leakage. [ABSTRACT FROM AUTHOR]