NLRP3 inflammasome-mediated pyroptosis contributes to the pathogenesis of non-ischemic dilated cardiomyopathy

Zeng, Cheng; Fu-jian, Duan; Hu, Jia; Luo, Baoming; Huang, Binlong; Lou, Xiaoying; Sun, Xiaochuan; Li, Hongyu; Zhang, Xuanhong; Yin, Shuo; Tan, Hongmei

doi:10.1016/j.redox.2020.101523

Cited by 235 publications

(177 citation statements)

References 43 publications

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“…Moreover, auranofin reduced expression of NOX4, which is a catalytic enzyme that could generate H 2 O 2 and mediates activation of NLRP3 inflammasome. Many studies also reported that NOX4 mediated in NLRP3 inflammasome formation [ 52 , 53 ]. HFD increased the expression of NLRP3 inflammasome and NOX4, and this mechanism was reduced by auranofin.…”

Section: Discussionmentioning

confidence: 99%

Auranofin Attenuates Non-Alcoholic Fatty Liver Disease by Suppressing Lipid Accumulation and NLRP3 Inflammasome-Mediated Hepatic Inflammation In Vivo and In Vitro

Hwangbo

Kim

et al. 2020

Antioxidants

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Non-alcoholic fatty liver disease (NAFLD) causes liver dysfunction and is associated with obesity and type 2 diabetes. Chronic inflammation is associated not only with the development of NAFLD, but also with hepatic diseases, including steatohepatitis, cirrhosis, and hepatocellular carcinoma. Auranofin is a treatment for rheumatoid arthritis and has recently been reported to have potential effects against a variety of diseases, including inflammation, cancer, and viral infection. In this study, auranofin may be considered as a new treatment for the management of metabolic syndrome, as well as in the treatment of NAFLD through immunomodulation. To determine the effect of auranofin on NAFLD, C57BL/6 mice were randomly grouped, fed a regular diet or a high fat diet (HFD), and injected with normal saline or auranofin for 8 weeks. Auranofin significantly decreased the body weight, epididymal fat weight, serum aspartate aminotransferase (AST), and glucose, as well as the serum triglyceride, cholesterol, and low-density lipoprotein cholesterol levels as compared to the HFD group. We also observed that hepatic steatosis was increased in the HFD group and was suppressed by auranofin treatment. In addition, auranofin suppressed the expressions of interleukin (IL)-1β, IL-18, caspase-1, and the NOD-like receptor family pyrin domain containing 3 (NLRP3) in the liver tissue. Furthermore, the expression of NADPH oxidase 4 and peroxisome proliferator-activated receptor γ (PPARγ), which are a major source of oxidative stress and a regulator of adipogenesis, respectively, were also decreased by auranofin. In addition, primary mouse hepatocytes were incubated with lipopolysaccharide (LPS) and palmitic acid (PA) to induce lipid accumulation and hepatic inflammation for an in vitro model. Auranofin could significantly inhibit LPS- and PA-induced inflammatory activity including nitric oxide and NLRP3 inflammasome-mediated cytokines. The results of this study demonstrate that auranofin treatment inhibits the characteristics of NAFLD through the inhibition of NLRP3 inflammasome. Therefore, auranofin may have potential as a candidate for improving NAFLD symptoms.

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Section: Discussionmentioning

confidence: 99%

Auranofin Attenuates Non-Alcoholic Fatty Liver Disease by Suppressing Lipid Accumulation and NLRP3 Inflammasome-Mediated Hepatic Inflammation In Vivo and In Vitro

Hwangbo

Kim

et al. 2020

Antioxidants

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“…BNIP3, the upstream regulator of cardiomyocyte pyroptosis, can activate caspase-3 and lead to subsequent GSDME cleavage (Zheng et al, 2020). DRP1/NOX signaling was activated to cause mitochondrial damage, which involved in DOX-induced pyrotosis (Zeng et al, 2020). Moreover, upregulated lncRNA TINCR recruited IGF2BP1 to enhance the NLRP3 expression that mediated Dox-induced pyrotosis (Meng et al, 2019).…”

Section: Pyroptosismentioning

confidence: 99%

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Wei

Zhang

et al. 2020

Front. Cell Dev. Biol.

108

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Homeostatic regulation of cardiomyocytes plays a crucial role in maintaining the normal physiological activity of cardiac tissue. Severe cardiotoxicity results in cardiac diseases including but not limited to arrhythmia, myocardial infarction and myocardial hypertrophy. Drug-induced cardiotoxicity limits or forbids further use of the implicated drugs. Such drugs that are currently available in the clinic include anti-tumor drugs (doxorubicin, cisplatin, trastuzumab, etc.), antidiabetic drugs (rosiglitazone and pioglitazone), and an antiviral drug (zidovudine). This review focused on cardiomyocyte death forms and related mechanisms underlying clinical drug-induced cardiotoxicity, including apoptosis, autophagy, necrosis, necroptosis, pryoptosis, and ferroptosis. The key proteins involved in cardiomyocyte death signaling were discussed and evaluated, aiming to provide a theoretical basis and target for the prevention and treatment of drug-induced cardiotoxicity in the clinical practice.

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“…NLRP3 inflammasome levels directly correlate with heart dysfunction, the levels of the N-terminal (NT) fragments of the pro-form of brain natriuretic peptide (BNP) (NT-proBNP, a marker of heart failure), and the rate of hospitalization in patients with dilated cardiomyopathy (DCM) [ 70 ]. Biopsies of DCM patients show increased cardiomyocyte pyroptosis [ 71 ].…”

Section: Role Of the Nlrp3 Inflammasome In The Development Of Cardmentioning

confidence: 99%

NLRP3 Inflammasome Inhibitors in Cardiovascular Diseases

2021

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Virtually all types of cardiovascular diseases are associated with pathological activation of the innate immune system. The NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is a protein complex that functions as a platform for rapid induction of the inflammatory response to infection or sterile injury. NLRP3 is an intracellular sensor that is sensitive to danger signals, such as ischemia and extracellular or intracellular alarmins during tissue injury. The NLRP3 inflammasome is regulated by the presence of damage-associated molecular patterns and initiates or amplifies inflammatory response through the production of interleukin-1β (IL-1β) and/or IL-18. NLRP3 activation regulates cell survival through the activity of caspase-1 and gasdermin-D. The development of NLRP3 inflammasome inhibitors has opened the possibility to targeting the deleterious effects of NLRP3. Here, we examine the scientific evidence supporting a role for NLRP3 and the effects of inhibitors in cardiovascular diseases.

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NLRP3 inflammasome-mediated pyroptosis contributes to the pathogenesis of non-ischemic dilated cardiomyopathy

Cited by 235 publications

References 43 publications

Auranofin Attenuates Non-Alcoholic Fatty Liver Disease by Suppressing Lipid Accumulation and NLRP3 Inflammasome-Mediated Hepatic Inflammation In Vivo and In Vitro

Auranofin Attenuates Non-Alcoholic Fatty Liver Disease by Suppressing Lipid Accumulation and NLRP3 Inflammasome-Mediated Hepatic Inflammation In Vivo and In Vitro

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

NLRP3 Inflammasome Inhibitors in Cardiovascular Diseases

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