NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin

Yue, Rongchuan; Zheng, Zaiyong; Luo, Yu; Wang, Xiaobo; Lv, Mingming; Qin, Dan; Tan, Qing‐Qing; Zhang, Yulong; Wang, Tao; Hu, Houxiang

doi:10.1038/s41420-021-00434-y

Cited by 68 publications

(47 citation statements)

References 48 publications

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“…Studies have shown that the NLRP3 inflammasome contributed to hepatic inflammation [ 58 , 59 ], but whether irisin has an effect on this pathway remains unclear. Recent findings showed that irisin exerts cardioprotective effects by inhibiting NLRP3-mediated pyroptosis [ 60 ]. However, in our study, we found that only NLRP3 inflammasome priming was triggered in HFD mice and attenuated by exercise, whereas the activity of the NLRP3 inflammasome in the cleavage of caspase-1 and GSDMD was unaltered.…”

Section: Discussionmentioning

confidence: 99%

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Zhu

Sahar

Javaid

et al. 2021

Cells

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Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and molecular mechanism of exercise on high-fat diet (HFD)-induced liver injury. In an HFD-induced NAFLD mouse model, exercise training significantly decreased hepatic steatosis and fibrosis. Interestingly, exercise training blocked the binding of MD2-TLR4 and decreased the downstream inflammatory response. Irisin is a myokine that is highly expressed in response to exercise and exerts anti-inflammatory effects. We found that circulating irisin levels and muscle irisin expression were significantly increased in exercised mice, suggesting that irisin could mediate the effect of exercise on NAFLD. In vitro studies showed that irisin improved lipid metabolism, fibrosis, and inflammation in palmitic acid (PA)-stimulated AML12 cells. Moreover, binding assay results showed that irisin disturbed MD2-TLR4 complex formation by directly binding with MD2 but not TLR4, and interfered with the recognition of stimuli such as PA and lipopolysaccharide with MD2. Our study provides novel evidence that exercise-induced irisin inhibits inflammation via competitive binding with MD2 to improve NAFLD. Thus, irisin could be considered a potential therapy for NAFLD.

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Section: Discussionmentioning

confidence: 99%

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Zhu

Sahar

Javaid

et al. 2021

Cells

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“…e underlying mechanism may be related to regulation with pyroptosis [26], mitochondrial function [27], and myofibroblast differentiation [28]. It is well established that NLRP3 inflammasome is upregulated in the process of MI [29,30].…”

Section: Discussionmentioning

confidence: 99%

LuQi Formula Ameliorates Myocardial Fibrosis by Suppressing TLR4/MyD88/NF-κB Pathway and NLRP3 Inflammasome Activation in Mice with Myocardial Infarction

Zhang

Yang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Myocardial fibrosis caused by myocardial infarction (MI) is the key factor leading to cardiac remodeling; nod-like receptor family pyrin domain-containing 3 (NLRP3) plays an important role in regulation of myocardial injury; however, its relationship with TLR4/MyD88/NF-κB signaling pathway is largely unreported. In recent years, traditional Chinese medicine (TCM) prevention and treatment of cardiovascular diseases has shown its unique advantages and broad application prospects. LuQi Formula (LQF) has been used for more than 20 years in Shuguang Hospital (Shanghai, China), and it was confirmed that it can improve the clinical symptoms of patients after MI. Here, we investigated the mechanism of LQF by suppressing NLRP3 inflammasome activation and TLR4/MyD88/NF-κB pathway in mice with MI. Purpose. The purpose of this study was to verify the positive effects of the LQF in ameliorating myocardial fibrosis and inflammasome infiltration in the MI mice in vivo. Methods. Forty mice were randomized into four groups: the sham group, the MI group, the LQF group, and the perindopril group (n = 10 per group). Left anterior descending (LAD) coronary artery ligation was performed in all groups except the sham group. The mice were treated with LQF after MI. After 4 weeks, LDH, cTnI, IL-1β, and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) kit, and cardiac function was evaluated by echocardiography. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the myocardial injury and fibrosis. Western blot was used to evaluate the expression of collagen I, α-SMA, NLRP3 inflammasome, and TLR4/MyD88/NF-κB signaling pathway. Immunohistochemical analysis was used to further detect the expression of Fibronectin, α-SMA, collagen I, collagen III, NLRP3, and NF-κB in myocardial tissue. Results. Compared with the MI group, the ejection fraction (EF) and fractional shortening (FS) in the LQF group were significantly improved, while the left ventricular end diastolic diameter (LVEDd) and left ventricular internal dimension systole (LVIDs) were significantly decreased. The representative staining of H&E and Masson showed that treatment with LQF could effectively reduce myocardial injury and fibrosis. ELISA results showed that serum LDH, cTnI, TNF-α, IL-18, and IL-1β in LQF group were significantly lower than those in MI group. The western blot results showed that the expressions of collagen I and α-SMA were decreased significantly in the LQF group. Moreover, the expressions of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathway were downregulated in the LQF treatment group. Conclusion. Our results suggested that LQF could significantly improve cardiac function and ameliorate myocardial fibrosis. In addition, we found that LQF could downregulate the TLR4/MyD88/NF-κB signaling pathway and then inhibit the activation of NLRP3 inflammasome, suggesting that LQF alleviated cardiac fibrosis by decreasing the TLR4/MyD88/NF-κB signaling pathway and then inhibited NLRP3 inflammasome activation in MI mice, which indicates potential therapeutic effect of LQF on patients with MI.

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“…Normally, moderate pyroptosis is conducive to the timely removal of infected cells. Nevertheless, excessive activation of pyroptosis leads to a large number of cell deaths and inflammatory cascade reactions, seriously damaging tissues and organs, and even leading to organ failure, which is closely related to the pathogenesis of certain diseases (75)(76)(77)(78)(79). A large number of studies have shown that pyroptosis is widely involved in the occurrence and progression of infectious diseases (80), metabolic diseases (81), tumors (82), nervous system diseases (83) and cardiovascular diseases (84).…”

Section: Role Of Pyroptosis In Diseasesmentioning

confidence: 99%

A Bibliometric Analysis of Pyroptosis From 2001 to 2021

et al. 2021

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BackgroundPyroptosis is a new programmed cell death discovered in recent years. Pyroptosis plays an important role in various diseases. Nevertheless, there are few bibliometric analysis systematically studies this field. We aimed to visualize the research hotspots and trends of pyroptosis using a bibliometric analysis to help understand the future development of basic and clinical research.MethodsThe articles and reviews regarding pyroptosis were culled from Web of Science Core Collection. Countries, institutions, authors, references and keywords in this field were visually analyzed by using CtieSpace and VOSviewer software.ResultsA total of 2845 articles and reviews were included. The number of articles regarding pyroptosis significantly increased yearly. These publications mainly come from 70 countries led by China and the USA and 418 institutions. We identified 605 authors, among which Thirumaladevi Kanneganti had the most significant number of articles, and Shi JJ was co-cited most often. Frontiers in immunology was the journal with the most studies, and Nature was the most commonly cited journal. After analysis, the most common keywords are nod like receptor family pyrin domain containing 3 inflammasome, apoptosis, cell death, gasdermin D, mechanism, caspase-1, and others are current and developing areas of study.ConclusionResearch on the pyroptosis is flourishing. Cooperation and exchanges between countries and institutions must be strengthened in the future. The related pathway mechanism of pyroptosis, the relationship between pyroptosis and other types of programmed cell deaths as well as the role of pyroptosis in various diseases have been the focus of current research and developmental trends in the future research.

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NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin

Cited by 68 publications

References 48 publications

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

LuQi Formula Ameliorates Myocardial Fibrosis by Suppressing TLR4/MyD88/NF-κB Pathway and NLRP3 Inflammasome Activation in Mice with Myocardial Infarction

A Bibliometric Analysis of Pyroptosis From 2001 to 2021

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