Therapeutic strategies in ischemic cardiomyopathy: Focus on mitochondrial quality surveillance

EBioMedicine, Journal Year: 2022, Volume and Issue: 84, P. 104260 - 104260

Published: Sept. 19, 2022

Language: Английский

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Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: May 24, 2023

Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents leading cause mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade pathophysiological events following restoration blood flow reoxygenation, not only directly damages brain tissue, but also enhances series pathological signaling cascades, contributing to inflammation, further aggravate damage tissue. Paradoxically, there are still no effective methods prevent CI/RI, since detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, characterized by mitochondrial oxidative stress, Ca 2+ overload, iron dyshomeostasis, DNA (mtDNA) defects quality control (MQC) disruption, closely relevant process CI/RI. There increasing evidence that dysfunctions play vital roles in regulation programmed cell deaths (PCDs) such as ferroptosis PANoptosis, newly proposed conception unique form innate immune inflammatory death regulated multifaceted PANoptosome complexes. In present review, we highlight how this key event contributes response well modes during Neuroprotective agents targeting may serve promising treatment strategy alleviate serious secondary injuries. A comprehensive insight into dysfunctions-mediated PCDs can help provide strategies guide therapies CI/RI IS.

Language: Английский

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Decreased MFN2 activates the cGAS-STING pathway in diabetic myocardial ischaemia–reperfusion by triggering the release of mitochondrial DNA

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 3, 2023

The cause of aggravation diabetic myocardial damage is yet to be elucidated; mitochondrial function has been a longstanding focus research. During ischaemia-reperfusion (MI/R), it remains unclear whether reduced fusion exacerbates injury by generating free damaged DNA (mitoDNA) and activating the cGAS-STING pathway.In this study, mouse model diabetes was established (by feeding mice high-fat diet (HFD) plus low dose streptozotocin (STZ)), MI/R cardiac ischaemia for 2 h reperfusion 30 min, cellular glycolipid toxicity induced high glucose (HG) palmitic acid (PA) in H9C2 cells.We observed that altered dynamics during led increased mitoDNA cytosol, activation pathway, phosphorylation downstream targets TBK1 IRF3. In we found cytosolic result HG PA, which also resulted signalling targets. Moreover, inhibition STING H-151 significantly ameliorated MFN2 knockdown both cell models. use fat-soluble antioxidant CoQ10 improved models.Our study elucidated critical role activation, triggered due decreased fusion, pathogenesis injury. This provides preclinical insights treatment Video Abstract.

Language: Английский

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Mitochondrial DNA leakage triggers inflammation in age-related cardiovascular diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 15, 2024

Mitochondrial dysfunction is one of the hallmarks cardiovascular aging. The leakage mitochondrial DNA (mtDNA) increased in senescent cells, which are resistant to programmed cell death such as apoptosis. Due its similarity prokaryotic DNA, mtDNA could be recognized by cellular sensors and trigger innate immune responses, resulting chronic inflammatory conditions during mechanisms include cGAS-STING signaling, TLR-9 inflammasomes activation. quality controls mitophagy prevent mitochondria from triggering harmful but when this homeostasis out balance, mtDNA-induced inflammation become pathogenic contribute age-related diseases. Here, we summarize recent studies on promotes aging-related diseases, discuss potential value early screening therapeutic targets.

Language: Английский

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Cell-free circulating mitochondrial DNA: An emerging biomarker for airborne particulate matter associated with cardiovascular diseases

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 195, P. 103 - 120

Published: Dec. 28, 2022

Language: Английский

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Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 15166 - 15166

Published: Dec. 2, 2022

The kidney is a mitochondria-rich organ, and diseases are recognized as mitochondria-related pathologies. Intact mitochondrial DNA (mtDNA) maintains normal function. Mitochondrial dysfunction caused by mtDNA damage, including impaired replication, mutation, leakage, methylation, involved in the progression of diseases. Herein, we review roles damage different setting diseases, acute injury (AKI) chronic disease (CKD). In variety closely associated with loss level peripheral serum urine also reflects status injury. Alleviating can promote recovery function exogenous drug treatment thus reduce short, conclude that may serve novel biomarker for assessing causes renal dysfunction, which provides new theoretical basis mtDNA-targeted intervention therapeutic option

Language: Английский

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OGG1 in the Kidney: Beyond Base Excision Repair

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 13

Published: Dec. 30, 2022

8-Oxoguanine DNA glycosylase (OGG1) is a repair protein for 8-oxoguanine (8-oxoG) in eukaryotic atopic DNA. Through the initial base excision (BER) pathway, 8-oxoG recognized and excised, subsequently, other proteins are recruited to complete repair. OGG1 primarily located cytoplasm can enter nucleus mitochondria damaged or exert epigenetic regulation of gene transcription. involved wide range physiological processes, such as repair, oxidative stress, inflammation, fibrosis, autophagy. In recent years, studies have found that plays an important role progression kidney diseases through repairing DNA, inducing regulating autophagy transcriptional regulation, governing interactions functions during disease injury. particular, effects gradually attracted widespread attention. This study reviews structure biological regulatory mechanism disease. addition, possibility potential therapeutic target discussed.

Language: Английский

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Artificial intelligence in assessing cardiovascular diseases and risk factors via retinal fundus images: A review of the last decade

Wiley Interdisciplinary Reviews Data Mining and Knowledge Discovery, Journal Year: 2024, Volume and Issue: 14(6)

Published: Oct. 9, 2024

Abstract Cardiovascular diseases (CVDs) are the leading cause of death globally. The use artificial intelligence (AI) methods—in particular, deep learning (DL)—has been on rise lately for analysis different CVD‐related topics. fundus images and optical coherence tomography angiography (OCTA) in diagnosis retinal has also extensively studied. To better understand heart function anticipate changes based microvascular characteristics function, researchers currently exploring integration AI with noninvasive scanning. There is great potential to reduce number cardiovascular events financial strain healthcare systems by utilizing AI‐assisted early detection prediction a large scale. A comprehensive search was conducted across various databases, including PubMed, Medline, Google Scholar, Scopus, Web Sciences, IEEE Xplore, ACM Digital Library, using specific keywords related AI. study included 87 English‐language publications selected relevance, additional references were considered. This article provides an overview recent developments difficulties imaging diagnose diseases. It insights further exploration this field. Researchers trying develop precise disease prognosis patterns response aging population growing global burden CVD. DL revolutionizing potentially diagnosing multiple CVDs from single image. However, swifter adoption these technologies required. categorized under: Application Areas > Health Care Technologies Artificial Intelligence

Language: Английский

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HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 22, 2022

HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in clinical setting. However, mechanism action components remains unclear. Ferroptosis critical factor that promotes myocardial I/R injury, pathophysiological ferroptosis-mediated lipid peroxidation causes injury. Therefore, this study explored whether decoction ameliorates by attenuating ACSL4-mediated ferroptosis. This also effect ACSL4 expression on iron-dependent programmed cell death preparing rat model oxygen glucose deprivation/reperfusion (OGD/R)-induced H9c2 cells. The results showed improved cardiac function; attenuated apoptosis, oxidative stress, mitochondrial damage, iron accumulation; reduced infarct size model. Additionally, suppressed ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) cyclooxygenase-2 (COX2)] but promoted ferroptosis-inhibiting [ferritin heavy chain 1 (FTH1) glutathione-dependent hydroperoxidase glutathione peroxidase (GPX4)] tissues Similar were found with OGD/R-induced Interestingly, knockdown accumulation, ferroptosis OGD/R-treated overexpression counteracted inhibitory OGD/R-triggered stress These findings suggest restrained development regulating Thus, may be an effective medication

Language: Английский

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Involvement of Oxidative Stress and Antioxidants in Modification of Cardiac Dysfunction Due to Ischemia–Reperfusion Injury

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 340 - 340

Published: March 14, 2025

Delayed reperfusion of the ischemic heart (I/R) is known to impair recovery cardiac function and produce a wide variety myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca2+-handling abnormalities, activation proteases, changes in gene expression. Although I/R injury has been reported induce formation reactive oxygen species (ROS), inflammation, intracellular Ca2+ overload, generation oxidative stress considered play critical role development dysfunction. Increases production superoxide, hydroxyl radicals, oxidants, such as hydrogen peroxide hypochlorous acid, occur hearts subjected injury. In fact, mitochondria are major source excessive ROS due impairment electron transport system well xanthine oxidase NADPH oxidase. Nitric oxide synthase, mainly present endothelium, also activated injury, leading nitric oxide, which, upon combination with superoxide generates nitrosative stress. Alterations function, sarcolemma, sarcoplasmic reticulum activities, mitochondrial phosphorylation, protease simulated exposing oxyradical-generating (xanthine plus oxidase) or H2O2. On other hand, endogenous antioxidants dismutase, catalase, glutathione peroxidase, concentration transcription factor (Nrf2), which modulates expression various antioxidants, depressed hearts. Furthermore, pretreatment catalase N-acetylcysteine, mercaptopropionylglycerine observed attenuate I/R-induced handling Ca2+-regulatory activities; additionally, it found depress improve function. These observations indicate that intimately involved pathological effects different alterations Thus, we faced task developing safe effective agents for upregulating therapy

Language: Английский

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