Beneficial effects of melatonin in juvenile rats with heart failure

2019 ◽  
Author(s):  
Yao Wu ◽  
Feifei Si ◽  
Li Luo ◽  
Fengchuan Jing ◽  
Kunfeng Jiang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Sham Group ◽  
Ventricular Dysfunction ◽  
Protective Role ◽  
Aortic Constriction ◽  
Juvenile Rats ◽  
Beneficial Effects ◽  
Abdominal Aortic

Abstract Background: Adult rodent studies showed that melatonin is very effective in treatment of ameliorating cardiovascular disease. Melatonin is also able to reduce cardiac hypertrophy and heart failure (HF) in juvenile rodents. Here, we study the effect of melatonin on the cardiac function of juvenile rats with HF. Methods: Juvenile rats with HF were induced by abdominal aortic constriction (AAC). Sham-operated rats were established in parallel. Five weeks after the surgery, rats with ventricular dysfunction were randomly divided into two groups: the treatment group was injected with melatonin (10 mg/kg/d, intraperitoneal injection), and the HF group was injected with placebo. Simultaneously, placebo was administered to the sham group. Results: After administration for 4 weeks, the treated rats did not exhibit a decline in cardiac function as assessed by echocardiography analysis. Moreover, the increase in expression of ANP, BNP, caspase-1, IL-1β, bax, CaMKII, PLN, and RyR2 was markedly blunted by melatonin, while the decrease in expression of bcl-2 was improved in the melatonin treated rats. Conclusions: Our findings support a protective role of melatonin in cardiomyocytes, at least in part via reducing cardiac pyroptosis, apoptosis and remaining calcium homeostasis.

Abstract 341: Protective Role of Myeloid Cell-specific Erbb3 Signaling After Transverse Aortic Constriction

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Haifeng Yin ◽  
Amanda J Lessard ◽  
Joanne T deKay ◽  
Yodit Herrmann ◽  
Michael P Robich ◽  
...  
Keyword(s):  
Heart Failure ◽  
Molecular Mechanisms ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Protective Role ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Cardiac Progenitors ◽  
Erbb3 Signaling

Introduction: Understanding molecular mechanisms underlying cardiac hypertrophy is crucial for protecting against cardiac remodeling, or slowing down its destined pathway to heart failure. Recent studies revealed that myeloid cells play an important role in the regulation of hypertrophic remodeling. Neuregulin-1 (NRG-1) has been shown to play an essential role in the regulation of tissue-protective and pro-survival processes in response to tissue injury in the cardiovascular system. We find that NRG-1 receptors, including ErbB2 and ErbB3, are expressed and functionally active in cardiac myeloid cells. We hypothesized that the NRG-1/ErbB3 signaling in myeloid cells plays a protective role in cardiac hypertrophic remodeling. To test this hypothesis, we examined the effect of Erbb3 gene ablation in mouse myeloid cells on cardiac hypertrophic remodeling induced by pressure overload. Methods and results: Myeloid-specific ErbB3-deficient mice (ErbB3 MyeKO ) were generated by crossing Erbb3 -floxed mice with LysM-Cre transgenic mice. Cardiac hypertrophic remodeling was established in mice by transverse aortic constriction (TAC). Five days after TAC, survival was dramatically reduced in male ErbB3 MyeKO mice (20% vs. 90%, p=0.021 , MyeKO vs. MyeWT). The post-mortem examination of lung weight to body weight ratio suggested that acute pulmonary edema was developed in ERBB3 MyeKO mice. In order to determine the cellular and molecular mechanisms involved in the increased mortality in ErbB3 MyeKO males, cardiac cell populations were examined at day 3 post-TAC using flow cytometry. A significant accumulation of myeloid cells was found in control but not in ErbB3 MyeKO males. This was accompanied by increased proliferation of Sca-1 positive non-immune cells (endothelial cells and cardiac progenitors) in control but not ErbB3 MyeKO males. An antibody-based protein array analysis revealed that IGF-1 expression was significantly downregulated only in ErbB3 MyeKO males after TAC. Conclusion: Our data highlight the important role of myeloid cell-specific ErbB3 signaling in the accumulation of myeloid cells that contributes to the development of compensatory hypertrophy and the prevention of acute heart failure in male mice.

scholarly journals Negative feedback of SNRK to circ-SNRK regulates cardiac function post-myocardial infarction

2021 ◽  
Author(s):  
Zhi-Yan Wang ◽  
Xiao-Xiao Liu ◽  
Yun-Fei Deng
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Negative Feedback ◽  
Atp Synthesis ◽  
Protective Role ◽  
Splicing Regulator ◽  
Mitochondrial Efficiency

AbstractA limited delivery of oxygen and metabolic substrate to the heart caused by myocardial infarction (MI) impairs the cardiac function, and often results in heart failure. Here, we identified a circRNA (circ-SNRK) from SNRK (sucrose nonfermenting 1-related kinase, which can increase the cardiac mitochondrial efficiency) in cardiomyocytes (CMs). Circ-SNRK can sponge the miR-33 and in turn improved the ATP synthesis via SNRK, proving the existence of circ-SNRK - miR-33 - SNRK axis. Furthermore, we found that protein NOVA1 (NOVA alternative splicing regulator 1) could accelerate the circ-SNRK formation; a cleaved peptide (~55 kDa) from SNRK enters the nucleus and blocks the cyclization of circ-SNRK via binding to NOVA1. The aforementioned negative feedback of SNRK to circ-SNRK limited the SNRK at a proper level, and inhibited the protective role of circ-SNRK in ischemic heart. In addition, our in vivo experiment indicated that the overexpression of exogenic circ-SNRK could break this loop and improves the cardiac function post-MI in rats. Together, our results demonstrated that the negative loop of circ-SNRK with SNRK regulates the energy metabolism in CMs, thus might be a potential therapeutic target for heart failure.

scholarly journals Ivabradine Ameliorates Cardiac Function in Heart Failure with Preserved and Reduced Ejection Fraction via Upregulation of miR-133a

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Shuai Shao ◽  
Yue Zhang ◽  
Mengqi Gong ◽  
Qian Yang ◽  
Meng Yuan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Mouse Models ◽  
Cardiac Fibroblasts ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Left Ventricular ◽  
Reduced Ejection Fraction

Heart failure (HF) is a clinical syndrome caused by impairment of ventricular filling, ejection of blood, or both and is categorized as HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF) based on left ventricular function. Cardiac fibrosis contributes to left ventricular dysfunction and leads to the development of HF. Ivabradine, an If current selective specific inhibitor, has been shown to improve the prognosis of patients with HF. However, the effects of ivabradine on cardiac function and fibrosis in HFpEF and HFrEF and the underlying mechanism remain unclear. In the present study, we utilized mouse models to mimic HFpEF and HFrEF and evaluated the therapeutic effects of ivabradine. By treating mice with different doses (10 mg/kg/d and 20 mg/kg/d) of ivabradine for 4 or 8 weeks, we found that a high dose of ivabradine improved cardiac diastolic function in HFpEF mice and ameliorated cardiac diastolic and systolic function and ventricular tachycardia incidence in HFrEF mice. Moreover, ivabradine significantly reduced the activation of cardiac fibroblasts and myocardial fibrosis in mice. Mechanistically, microRNA-133a, which was upregulated by ivabradine, targeted connective tissue growth factor and collagen 1 in cardiac fibroblasts and might contribute to the protective role of ivabradine. Together, our work utilized mouse models to study HFpEF and HFrEF, demonstrated the protective role of ivabradine in HFpEF and HFrEF, and elucidated the potential underlying mechanism, which provides an effective strategy for related diseases.

Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq
Keyword(s):  
Heart Failure ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Galectin 3 ◽  
Consequent Increase ◽  
And Oxidative Stress

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

scholarly journals Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Intercellular Adhesion Molecule ◽  
Intestinal Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Beneficial Effects ◽  
Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

scholarly journals Possible Protective Role of Melatonin in Pediatric Infectious Diseases and Neurodevelopmental Pathologies

2020 ◽  
Vol 10 (01) ◽  
pp. e104-e109
Author(s):  
Antonio Molina-Carballo ◽  
Antonio Emilio Jerez-Calero ◽  
Antonio Muñoz-Hoyos
Keyword(s):  
Endothelial Cell ◽  
Free Radical ◽  
Chronic Administration ◽  
Protective Role ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Energetic Metabolism ◽  
Beneficial Effects ◽  
Molecular Crosstalk

AbstractMelatonin, produced in every cell that possesses mitochondria, acts as an endogenous free radical scavenger, and improves energetic metabolism and immune function, by complex molecular crosstalk with other intracellular compounds. There is greatly increasing evidence regarding beneficial effects of acute and chronic administration of high melatonin doses, in infectious, developmental, and degenerative pathologies, as an endothelial cell and every cell protectant.

scholarly journals The Protective Role of Butyrate against Obesity and Obesity-Related Diseases

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 682
Author(s):  
Serena Coppola ◽  
Carmen Avagliano ◽  
Antonio Calignano ◽  
Roberto Berni Canani
Keyword(s):  
Metabolic Diseases ◽  
Environmental Changes ◽  
Short Chain Fatty Acids ◽  
Protective Role ◽  
Health Concern ◽  
Predisposing Factor ◽  
Alcoholic Fatty Liver ◽  
Beneficial Effects ◽  
The Individual

Worldwide obesity is a public health concern that has reached pandemic levels. Obesity is the major predisposing factor to comorbidities, including type 2 diabetes, cardiovascular diseases, dyslipidemia, and non-alcoholic fatty liver disease. The common forms of obesity are multifactorial and derive from a complex interplay of environmental changes and the individual genetic predisposition. Increasing evidence suggest a pivotal role played by alterations of gut microbiota (GM) that could represent the causative link between environmental factors and onset of obesity. The beneficial effects of GM are mainly mediated by the secretion of various metabolites. Short-chain fatty acids (SCFAs) acetate, propionate and butyrate are small organic metabolites produced by fermentation of dietary fibers and resistant starch with vast beneficial effects in energy metabolism, intestinal homeostasis and immune responses regulation. An aberrant production of SCFAs has emerged in obesity and metabolic diseases. Among SCFAs, butyrate emerged because it might have a potential in alleviating obesity and related comorbidities. Here we reviewed the preclinical and clinical data that contribute to explain the role of butyrate in this context, highlighting its crucial contribute in the diet-GM-host health axis.

Abstract 123: SUMO1 Modification Regulates SR Calcium ATPase Pump, SERCA2a in Heart Failure

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Changwon Kho ◽  
Ahyoung Lee ◽  
Dongtak Jeong ◽  
Jae Gyun Oh ◽  
Antoine Chaanine ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Calcium Atpase ◽  
Post Translational Modifications ◽  
Beneficial Effects ◽  
Protein Levels ◽  
In Trans ◽  
Underlying Mechanisms ◽  
Hemodynamic Performance ◽  
Reduced Activity

Background: The cardiac calcium ATPase, SERCA2a, is a critical pump responsible for Ca2+ re-uptake during excitation-contraction coupling. Impaired Ca2+ uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure. Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients, as well as in animal models. However, the underlying mechanisms of SERCA2a’s dysfunction remain incompletely understood. Methods and Results: In this study, we show that SERCA2a is modified by SUMO1 at lysine sites 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. SUMO1 and SERCA2a SUMOylation levels were both decreased in mouse and pig models of heart failure and failing human left ventricles. To determine whether reduced SUMO1 levels are responsible for reduced SERCA2a protein levels and reduced cardiac function, we used an adenovirus associated virus-mediated gene delivery approach to up-regulate SUMO1 in trans aortic constriction-induced mouse model of heart failure. We found that increasing SUMO1 levels led to a restoration of SERCA2a levels, improved hemodynamic performance, and reduced mouse mortality. By contrast, down-regulation of SUMO1 using small hairpin RNA accelerated cardiac functional deterioration and was accompanied by decreased SERCA2a function. Conclusion: In this study, we study a new mechanism for modulation of SERCA2a activity and beneficial effects of SUMO1 in the setting of heart failure. It suggests that changes in post-translational modifications of SERCA2a could negatively affect cardiac function in heart failure. Our data may provide a new platform for the design of therapeutic strategies for heart failure.

scholarly journals Cardiac Protection of Valsartan on Juvenile Rats with Heart Failure by Inhibiting Activity of CaMKII via Attenuating Phosphorylation

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Yao Wu ◽  
Feifei Si ◽  
Xiaojuan Ji ◽  
Kunfeng Jiang ◽  
Sijie Song ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Myocyte ◽  
Pressure Overload ◽  
The Other ◽  
Calcium Handling ◽  
Juvenile Rats ◽  
Abdominal Aortic ◽  
Calcium Handling Proteins ◽  
Increased Activity ◽  
Induce Heart Failure

Background. This study was undertaken to determine relative contributions of phosphorylation and oxidation to the increased activity of calcium/calmodulin-stimulated protein kinase II (CaMKII) in juveniles with cardiac myocyte dysfunction due to increased pressure overload. Methods. Juvenile rats underwent abdominal aortic constriction to induce heart failure. Four weeks after surgery, rats were then randomly divided into two groups: one group given valsartan (HF + Val) and the other group given placebo (HF + PBO). Simultaneously, the sham-operated rats were randomly given valsartan (Sham + Val) or placebo (Sham + PBO). After 4 weeks of treatment, Western blot analysis was employed to quantify CaMKII and relative calcium handling proteins (RyR2 and PLN) in all groups. Results. The deteriorated cardiac function was reversed by valsartan treatment. In ventricular muscle cells of group HF + PBO, Thr287 phosphorylation of CaMKII and S2808 phosphorylation of RyR2 and PLN were increased and S16 phosphorylation of PLN was decreased compared to the other groups, while Met281 oxidation was not significantly elevated. In addition, these changes in the expression of calcium handling proteins were ameliorated by valsartan administration. Conclusions. The phosphorylation of Thr286 is associated with the early activation of CaMKII rather than the oxidation of Met281.

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