scholarly journals Oxidative Stress-Responsive MicroRNAs in Heart Injury

2020 ◽  
Vol 21 (1) ◽  
pp. 358 ◽  
Author(s):  
Branislav Kura ◽  
Barbara Szeiffova Bacova ◽  
Barbora Kalocayova ◽  
Matus Sykora ◽  
Jan Slezak
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Ischemia Reperfusion Injury ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Stress Oxidative ◽  
Living Organisms

Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many signaling pathways. However, if overproduced, they also play a significant role in the development of cardiovascular diseases, such as arrhythmia, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction and heart transplantation), and heart failure. As a result of oxidative stress action, apoptosis, hypertrophy, and fibrosis may occur. MicroRNAs (miRNAs) represent important endogenous nucleotides that regulate many biological processes, including those involved in heart damage caused by oxidative stress. Oxidative stress can alter the expression level of many miRNAs. These changes in miRNA expression occur mainly via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, calcineurin/nuclear factor of activated T cell (NFAT), or nuclear factor kappa B (NF-κB) pathways. Up until now, several circulating miRNAs have been reported to be potential biomarkers of ROS-related cardiac diseases, including myocardial infarction, hypertrophy, ischemia/reperfusion, and heart failure, such as miRNA-499, miRNA-199, miRNA-21, miRNA-144, miRNA-208a, miRNA-34a, etc. On the other hand, a lot of studies are aimed at using miRNAs for therapeutic purposes. This review points to the need for studying the role of redox-sensitive miRNAs, to identify more effective biomarkers and develop better therapeutic targets for oxidative-stress-related heart diseases.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

scholarly journals Immune‐Responsive Gene 1/Itaconate Activates Nuclear Factor Erythroid 2–Related Factor 2 in Hepatocytes to Protect Against Liver Ischemia–Reperfusion Injury

Hepatology ◽  
2020 ◽  
Vol 72 (4) ◽  
pp. 1394-1411 ◽  
Author(s):  
Zhongjie Yi ◽  
Meihong Deng ◽  
Melanie J. Scott ◽  
Guang Fu ◽  
Patricia A. Loughran ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Liver Ischemia ◽  
Responsive Gene

scholarly journals Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs

Circulation ◽  
2020 ◽  
Vol 142 (9) ◽  
pp. 868-881 ◽  
Author(s):  
Andrea Baehr ◽  
Kfir Baruch Umansky ◽  
Elad Bassat ◽  
Victoria Jurisch ◽  
Katharina Klett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Single Dose ◽  
Matrix Protein ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Heart Function ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Extracellular Matrix Protein ◽  
Number Of Patients

Background: Ischemic heart diseases are leading causes of death and reduced life quality worldwide. Although revascularization strategies significantly reduce mortality after acute myocardial infarction (MI), a large number of patients with MI develop chronic heart failure over time. We previously reported that a fragment of the extracellular matrix protein agrin promotes cardiac regeneration after MI in adult mice. Methods: To test the therapeutic potential of agrin in a preclinical porcine model, we performed ischemia–reperfusion injuries using balloon occlusion for 60 minutes followed by a 3-, 7-, or 28-day reperfusion period. Results: We demonstrated that local (antegrade) delivery of recombinant human agrin to the infarcted pig heart can target the affected regions in an efficient and clinically relevant manner. A single dose of recombinant human agrin improved heart function, infarct size, fibrosis, and adverse remodeling parameters 28 days after MI. Short-term MI experiments along with complementary murine studies revealed myocardial protection, improved angiogenesis, inflammatory suppression, and cell cycle reentry as agrin’s mechanisms of action. Conclusions: A single dose of agrin is capable of reducing ischemia–reperfusion injury and improving heart function, demonstrating that agrin could serve as a therapy for patients with acute MI and potentially heart failure.

scholarly journals The Cardioprotective Actions of Hydrogen Sulfide in Acute Myocardial Infarction and Heart Failure

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
David J. Polhemus ◽  
John W. Calvert ◽  
Javed Butler ◽  
David J. Lefer
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Hydrogen Sulfide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Multiple Organ ◽  
Organ Systems ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

It has now become universally accepted that hydrogen sulfide (H2S), previously considered only as a lethal toxin, has robust cytoprotective actions in multiple organ systems. The diverse signaling profile of H2S impacts multiple pathways to exert cytoprotective actions in a number of pathological states. This paper will review the recently described cardioprotective actions of hydrogen sulfide in both myocardial ischemia/reperfusion injury and congestive heart failure.

scholarly journals NETosis as a Pathogenic Factor for Heart Failure

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Shuang Ling ◽  
Jin-Wen Xu
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Bacterial Infections ◽  
Defense Mechanism ◽  
Tissue Injury ◽  
Heart Diseases ◽  
Immune Defense ◽  
Low Grade ◽  
Aseptic Inflammation

Heart failure threatens the lives of patients and reduces their quality of life. Heart failure, especially heart failure with preserved ejection fraction, is closely related to systemic and local cardiac persistent chronic low-grade aseptic inflammation, microvascular damage characterized by endothelial dysfunction, oxidative stress, myocardial remodeling, and fibrosis. However, the initiation and development of persistent chronic low-grade aseptic inflammation is unexplored. Oxidative stress-mediated neutrophil extracellular traps (NETs) are the main immune defense mechanism against external bacterial infections. Furthermore, NETs play important roles in noninfectious diseases. After the onset of myocardial infarction, atrial fibrillation, or myocarditis, neutrophils infiltrate the damaged tissue and aggravate inflammation. In tissue injury, damage-related molecular patterns (DAMPs) may induce pattern recognition receptors (PRRs) to cause NETs, but whether NETs are directly involved in the pathogenesis and development of heart failure and the mechanism is still unclear. In this review, we analyzed the markers of heart failure and heart failure-related diseases and comorbidities, such as mitochondrial DNA, high mobility box group box 1, fibronectin extra domain A, and galectin-3, to explore their role in inducing NETs and to investigate the mechanism of PRRs, such as Toll-like receptors, receptor for advanced glycation end products, cGAS-STING, and C-X-C motif chemokine receptor 2, in activating NETosis. Furthermore, we discussed oxidative stress, especially the possibility that imbalance of thiol redox and MPO-derived HOCl promotes the production of 2-chlorofatty acid and induces NETosis, and analyzed the possibility of NETs triggering coronary microvascular thrombosis. In some heart diseases, the deletion or blocking of neutrophil-specific myeloperoxidase and peptidylarginine deiminase 4 has shown effectiveness. According to the results of current pharmacological studies, MPO and PAD4 inhibitors are effective at least for myocardial infarction, atherosclerosis, and certain autoimmune diseases, whose deterioration can lead to heart failure. This is essential for understanding NETosis as a therapeutic factor of heart failure and the related new pathophysiology and therapeutics of heart failure.

scholarly journals AMPK/SIRT1 Pathway is Involved in Arctigenin-Mediated Protective Effects Against Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Cheng-Yin Liu ◽  
Yi Zhou ◽  
Tao Chen ◽  
Jing-Chao Lei ◽  
Xue-Jun Jiang
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Arctigenin, one of the active ingredients extracted from Great Burdock (Arctium lappa) Achene, has been found to relieve myocardial infarction injury. However, the specific mechanism of Arctigenin against myocardial infarction remains largely unknown. Here, both acute myocardial ischemia-reperfusion injury (AMI/R) rat model and oxygen glucose deprivation (OGD)-induced myocardial cell injury model were constructed to explore the underlying role of AMPK/SIRT1 pathway in Arctigenin-mediated effects. The experimental data in our study demonstrated that Arctigenin ameliorated OGD-mediated cardiomyocytes apoptosis, inflammation and oxidative stress in a dose-dependent manner. Besides, Arctigenin activated AMPK/SIRT1 pathway and downregulated NF-κB phosphorylation in OGD-treated cardiomyocytes, while inhibiting AMPK or SIRT1 by the Compound C (an AMPK inhibitor) or SIRT1-IN-1 (a SIRT1 inhibitor) significantly attenuated Arctigenin-exerted protective effects on cardiomyocytes. In the animal experiments, Arctigenin improved the heart functions and decreased infarct size of the AMI/R-rats, accompanied with downregulated oxidative stress, inflammation and apoptotic levels in the heart tissues. What’s more, Arctigenin enhanced the AMPK/SIRT1 pathway and repressed NF-κB pathway activation. Taken together, our data indicated that Arctigenin reduced cardiomyocytes apoptosis against AMI/R-induced oxidative stress and inflammation at least via AMPK/SIRT1 pathway.

Diosmetin Ameliorates Cerebral Ischemia/Reperfusion Injury in PC12 Cells Through Nuclear Factor-kB (NF-kB) and Nuclear Factor Erythroid 2-Related Factor/Heme Oxygenase-1 (Nrf 2/HO-1) Pathway

2019 ◽  
Vol 17 (3) ◽  
pp. 322-328
Author(s):  
Luan Lan ◽  
Cao Lanxiu ◽  
Zhu Lei ◽  
Sun Jianhua
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Pc12 Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Diosmetin, a natural flavonoid, exhibits a variety of pharmacologic activities including inhibition of inflammation and oxidation. Therefore, its potential role in the management of cerebral ischemia/reperfusion (I/R) injury remains to be examined. In this study, we explored the underlying molecular mechanisms of diosmetin effects on cerebral ischemia/reperfusion injury in vitro. The results show that hypoxia/reoxygenation treatment of PC12 cells decreased cell viability and increased apoptosis, inflammation and oxidative stress. Diosmetin improved cellular viability, decreased lactate dehydrogenase release, and inhibited apoptosis in hypoxia-/reoxygenation-treated PC12 cells. Furthermore, diosmetin effectively inhibited the NF-kB signaling pathway to attenuate the inflammatory response. Also, diosmetin inhibited reactive oxygen species generation to attenuate I/R injury-induced oxidative stress in PC12 cells probably through the activation of Nrf 2/HO-1 pathway. Therefore, diosmetin effectively protected cells from I/R injury in nerve cells by scavenging reactive oxygen species by activating Nrf 2/HO-1 pathway and inhibiting inflammation by the suppression of NF-kB signaling pathway. Diosmetin can be regarded as a potential agent for cerebral ischemia/reperfusion injury treatment.

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