Targeting the NLRP3 Inflammasome in Severe COVID-19

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Июнь 23, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the genus Betacoronavirus within family Coronaviridae. It an enveloped single-stranded positive-sense RNA virus. Since December 2019, global expansion infection has occurred with widespread dissemination disease 2019 (COVID-19). COVID-19 often manifests as only mild cold-like symptomatology, but severe complications occurs in 15% cases. Respiratory failure that can be accompanied by systemic inflammatory reaction characterized cytokine release. In cases, fatality caused rapid development lung injury characteristic distress (ARDS). Although ARDS complication SARS-CoV-2 infection, it not viral replication or causes tissue injury; rather, result dysregulated hyperinflammation response to infection. This pathology intense, stimulation innate immune triggers activation Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway and release its products including proinflammatory cytokines IL-6 IL-1β. Here we review literature describes pathogenesis NLRP3 describe important role targeting this for treatment COVID-19.

Язык: Английский

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Metabolic syndrome and cardiovascular diseases: Going beyond traditional risk factors

Diabetes/Metabolism Research and Reviews, Год журнала: 2021, Номер 38(3)

Опубликована: Окт. 8, 2021

Metabolic syndrome (MS) is a chronic non-infective characterised clinically by set of vascular risk factors that include insulin resistance, hypertension, abdominal obesity, impaired glucose metabolism, and dyslipidaemia. These are due to pro-inflammatory state, oxidative stress, haemodynamic dysfunction, ischaemia, which overlap in 'dysmetabolic' patients. This review aimed evaluate the relationship between traditional components MS with cardiovascular disease (CVD), inflammation, stress. MEDLINE-PubMed, EMBASE, Cochrane databases were searched. Chronic low-grade inflammatory states metaflammation often accompanied metabolic changes directly related CVD incidence, such as diabetes mellitus, obesity. Moreover, an increase serum concentration cytokines, mainly interleukin-1 β (IL-1β), IL-6, tumour necrosis factor-α (TNF-α), originating from chronically inflamed adipose tissue associated The reactive oxygen species overloads antioxidant systems causing post-translational alterations proteins, lipids, DNA leading Hyperglycaemia contributes stress production advanced glycosylation end products (AGEs) cellular molecular dysfunction. Oxidative inflammation senescence CVD. should not be seen only being triggered classical factors. Atherosclerosis multifactorial pathological process several triggering aetiopathogenic mechanisms. Its medium long-term repercussions, however, invariably constitute significant cause morbidity mortality. Implementing preventive therapeutic measures against oxy-reductive imbalances has unquestionable potential for favourable clinical outcomes medicine.

Язык: Английский

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Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: The role of the ERK-CREB pathway and Bnip3-mediated mitophagy

Redox Biology, Год журнала: 2018, Номер 18, С. 229 - 243

Опубликована: Июль 21, 2018

Increased mitochondrial damage is related to the progression of a diet-induced nonalcoholic fatty liver disease. The aim our study investigate role Sirtuin 3 (Sirt3) in treating disease with focus on mitophagy and ERK-CREB pathway. Our data indicated that Sirt3 was downregulated tissue response chronic HFD treatment. Interestingly, re-introduction protected hepatic function, attenuated fibrosis, alleviated inflammatory response, prevented hepatocyte apoptosis. Molecular investigations demonstrated lipotoxicity associated an increase apoptosis as evidenced by reduced potential, augmented ROS production, increased cyt-c leakage into nucleus, activated caspase-9 apoptotic signalling. Additionally, overexpression hepatocytes against via promoting Bnip3-required mitophagy. Functional studies showed reversed Bnip3 expression activity signalling Blockade axis repressed promotive effects activation augmentation, finally negating anti-apoptotic influences setting high-fat-stress. Collectively, show high-fat-mediated downregulation, which followed pathway inactivation Bnip3-mediated inhibition mitophagy, causing undergo mitochondria-dependent cell death. Based this, strategies for enhancing activating ERK-CREB-Bnip3-mitophagy pathways could be used treat

Язык: Английский

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Mitochondrial quality control mechanisms as molecular targets in cardiac ischemia–reperfusion injury

Acta Pharmaceutica Sinica B, Год журнала: 2020, Номер 10(10), С. 1866 - 1879

Опубликована: Апрель 9, 2020

Mitochondrial damage is a critical contributor to cardiac ischemia/reperfusion (I/R) injury. quality control (MQC) mechanisms, series of adaptive responses that preserve mitochondrial structure and function, ensure cardiomyocyte survival function after I/R MQC includes fission, fusion, mitophagy mitochondria-dependent cell death. The interplay among these linked pathological changes such as redox imbalance, calcium overload, energy metabolism disorder, signal transduction arrest, the unfolded protein response endoplasmic reticulum stress. Excessive fission an early marker Reduced fusion has been observed in stressed cardiomyocytes correlates with dysfunction depression. Mitophagy allows autophagosomes selectively degrade poorly structured mitochondria, thus maintaining network fitness. Nevertheless, abnormal maladaptive Although mitochondria serve fuel source heart by continuously producing adenosine triphosphate, they also stimulate death inducing apoptosis or necroptosis reperfused myocardium. Therefore, defects may determine fate cardiomyocytes. In this review, we summarize regulatory mechanisms effects myocardial injury, highlighting potential targets for clinical management reperfusion.

Язык: Английский

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Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway

Aging, Год журнала: 2020, Номер 12(23), С. 24270 - 24287

Опубликована: Ноя. 21, 2020

Ischemia/reperfusion (I/R) injury is a life-threatening vascular emergency following myocardial infarction. Our previous study showed cardioprotective effects of metformin against I/R injury. In this study, we further examined the involvement AMPK mediated activation NLRP3 inflammasome in effect metformin. Myocardial was simulated rat heart Langendorff model and neonatal ventricle myocytes (NRVMs) were subjected to hypoxi/reoxygenation (H/R) establish an vitro model. Outcome measures included infarct size, hemodynamic monitoring, tissue injury, apoptotic index inflammatory response. size cardiac enzyme activities. First, found that postconditioning can not only significantly alleviated attenuated cell apoptosis, inhibited fibrosis. Furthermore, activated phosphorylated AMPK, decreased pro-inflammatory cytokines, TNF-α, IL-6 IL-1β, activation. isolated NRVMs increased cellular viability, LDH activity apoptosis inflammation. Importantly, inhibition phosphorylation by Compound C (CC) resulted survival cardiomyocytes mainly inducing release cytokines increasing Finally, studies revealed activator nigericin abolished anti-inflammatory NRVMs, but it had little on phosphorylation. Collectively, our confirmed exerts regulating injury-induced response, which largely dependent enhancement pathway, thereby suppressing

Язык: Английский

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M2 macrophage-derived exosomes carry microRNA-148a to alleviate myocardial ischemia/reperfusion injury via inhibiting TXNIP and the TLR4/NF-κB/NLRP3 inflammasome signaling pathway

Journal of Molecular and Cellular Cardiology, Год журнала: 2020, Номер 142, С. 65 - 79

Опубликована: Фев. 20, 2020

Язык: Английский

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ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 23

Опубликована: Окт. 19, 2022

Reactive oxygen species (ROS) are bioproducts of cellular metabolism. There is a range molecules with oxidizing properties known as ROS. Despite those being implied negatively in aging and numerous diseases, their key role signaling evident. ROS control several biological processes such inflammation, proliferation, cell death. The redox underlying these events one characteristic the new generation scientists aimed at defining environment. potential, which includes balance sources antioxidant system, implies an important target for understanding cells’ fate derived from signaling. In this review, we summarized chemical, balance, signaling, implications aging.

Язык: Английский

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Mitochondrial quality control in cardiac microvascular ischemia-reperfusion injury: New insights into the mechanisms and therapeutic potentials

Pharmacological Research, Год журнала: 2020, Номер 156, С. 104771 - 104771

Опубликована: Март 28, 2020

Язык: Английский

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COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches

GeroScience, Год журнала: 2020, Номер 42(4), С. 1021 - 1049

Опубликована: Май 20, 2020

Язык: Английский

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NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice

Aging Cell, Год журнала: 2019, Номер 19(1)

Опубликована: Окт. 18, 2019

Abstract While NLRP3‐inflammasome has been implicated in cardiovascular diseases, its role physiological cardiac aging is largely unknown. During aging, many alterations occur the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated molecular mechanisms through NLRP3 inhibition may attenuate aging. Ablation protected mice from age‐related increased sensitivity, reduced IGF‐1 leptin/adiponectin ratio levels, damage protection prolongation age‐dependent PR interval, atrial fibrillation by telomere shortening. Furthermore, old KO showed an PI3K/AKT/mTOR pathway improvement, compared wild preserved Nampt‐mediated NAD + levels SIRT1 protein expression. These findings suggest that suppression prevented age‐associated changes heart, function aged lifespan.

Язык: Английский

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