Pyroptosis: A New Regulating Mechanism in Cardiovascular Disease

Ji, Nan; Qi, Zhongwen; Wang, Yueyao; Yang, Xinggang; Yan, Zhipeng; Li, Meng; Ge, Qihui; Zhang, Junping

doi:10.2147/jir.s308177

Cited by 84 publications

(74 citation statements)

References 124 publications

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“…An important characteristic of P2X7 is that the non-selective ion channels will open under the action of high extracellular ATP concentration, allowing macromolecules to pass through, and leading to the formation of NLRP3 inflammasome ( Yin et al, 2017 ; Zhou et al, 2021 ) NLRP3 is closely associated with MIRI ( Hu et al, 2019 ). NLRP3 can promote the release of inflammatory mediators from cardiomyocytes, such as IL-1β and IL-18, and induce pyroptosis ( Ji et al, 2021 ). Pyroptosis is frequently involved in the development of atherosclerotic heart disease, infectious diseases and nervous system-related diseases, that are characterized by the formation of inflammasome, the activation of gasdermin and caspase-1, and the release of pro-inflammatory factors.…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis

Cai

et al. 2021

Front. Mol. Biosci.

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Myocardial ischemia is common in aging population. This study investigates the protective effect of Sevoflurane on myocardial ischemia reperfusion injury (MIRI) and its underlying mechanism. A total of 87 patients with a history of myocardial ischemia who underwent abdominal surgery with Sevoflurane general anesthesia were recruited in the study. The clinical data, blood pressure, heart rate, pressure-rate quotient (PRQ) and rate-pressure product (RPP) were recorded. Serum samples were collected and heart-type fatty acid binding protein (H-FABP), ischemia modified albumin (IMA), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were measured to observe whether Sevoflurane anesthesia had protective effect on myocardium. In addition, MIRI rats and hypoxia/reoxygenation (H/R) injury cell model was established using neonatal rat ventricular myocytes (NRVM). Rats or NRVM were pretreated with sevoflurane for 45min before hypoxia. The mRNA expression of purinergic receptor-7 (P2X7) and NLR family pyrin domain containing 3(NLRP3) were examined. The protein expression of P2X7, NLRP3, apoptosis-associated speck-like protein (ASC), cysteine aspartic acid specific protease-1(Caspase-1), Gasdermin-D (GSDMD), Bcl-2 Associated X Protein (Bax), B-cell lymphoma-2 (Bcl-2) in myocardial tissue and cells were evaluated. The serum contents of IL-1β, IL-18, Malondialdehyde (MDA), Superoxide dismutase (SOD), Lactate dehydrogenase (LDH), Creatine kinase (CK), and Creatine kinase isoenzymes (CK-MB) were measured. The cellular localization and fluorescence intensity of NLRP3 and ASC in cells were detected. It was found that the secretion of IL-1β and IL-18 decreased in the patients. After I45 min/R3h in SD rats and H3h/R1h in NRVM, the protein expressions of P2X7, NLRP3, ASC, Caspase-1 and GSDMD were increased, the release of IL-1β, IL-18, CK, CK-MB, LDH and MDA were increased, and SOD activity was decreased. Sevoflurane treatment inhibited the high expression of P2X7, NLRP3, ASC, Caspase-1 and GSDMD, inhibited the release of LDH, CK,CK-MB and MDA in cells, and improved the activity of SOD, indicating that Sevoflurane alleviated the damage of MIRI of rats and H/R of NRVM, and had myocardial protective effect. Taken together, our study suggests that Sevoflurane inhibited the expression of IL-1β, IL-18 and GSDMD by inhibiting the P2X7-NLRP3 signaling pathway. It reduced the H/R injury of cardiomyocytes and protected the cardiac function by regulating inflammatory reaction and pyroptosis.

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Section: Introductionmentioning

confidence: 99%

Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis

Cai

et al. 2021

Front. Mol. Biosci.

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“…The PI3K/Akt signaling pathway is an important pathway by which ginsenosides improve apoptosis. The activation of this pathway promotes angiogenesis, alleviates tissue hypoxia, suppresses cell damage, and improves MC apoptosis (Wang M. et al, 2021;Cao et al, 2021). Evidence showed that ginsenoside Rb1, Rb3, Rb2/Rb3 combination, Rd, Rg1, Rg2, Rg3, Rh1, Rh2, Rk3 activated the PI3K/Akt-mediated signaling pathway (Supplementary Table S1).…”

Section: Pi3k/akt-mediated Signaling Pathwaymentioning

confidence: 99%

“…Thirdly, evidence showed that pyroptosis occurred during the development of MIRI ( Xu XN. et al, 2021 ; Ji et al, 2021 ), and pro-apoptotic caspase-3 can cleave GSDME to induce pyroptosis ( Wang Y. et al, 2017 ). However, no study has confirmed the anti-pyroptosis effect of ginsenosides in improving MIRI.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury

Chen

et al. 2022

Front. Pharmacol.

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Ischemic heart disease has a high mortality, and the recommended therapy is reperfusion. Nevertheless, the restoration of blood flow to ischemic tissue leads to further damage, namely, myocardial ischemia/reperfusion injury (MIRI). Apoptosis is an essential pathogenic factor in MIRI, and ginsenosides are effective in inhibiting apoptosis and alleviating MIRI. Here, we reviewed published studies on the anti-apoptotic effects of ginsenosides and their mechanisms of action in improving MIRI. Each ginsenoside can regulate multiple pathways to protect the myocardium. Overall, the involved apoptotic pathways include the death receptor signaling pathway, mitochondria signaling pathway, PI3K/Akt signaling pathway, NF-κB signaling pathway, and MAPK signaling pathway. Ginsenosides, with diverse chemical structures, regulate different apoptotic pathways to relieve MIRI. Summarizing the effects and mechanisms of ginsenosides contributes to further mechanism research studies and structure–function relationship research studies, which can help the development of new drugs. Therefore, we expect that this review will highlight the importance of ginsenosides in improving MIRI via anti-apoptosis and provide references and suggestions for further research in this field.

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“…The former could trigger cell swelling, cell rupture, and promote the inflammation. 10 , 11 Besides, other important role of activated caspase-1 is to induce the ripeness and release of IL-18 and IL-1β, which have ability to aggregate inflammatory response. 12 Recently, pyroptosis has become a new topic in cancer research, many studies found that pyroptosis plays an essential regulator in tumor invasion, proliferation and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia

Liu¹,

Luo²,

Luo³

et al. 2022

IJGM

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Background Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis and prognosis in AML remained less understood. Methods We downloaded three public datasets and constructed a signature of TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the overall survival of AML patients. Samples from the GEO database were treated as a validation cohort. Gone through LASSO-Cox regression analysis, an 8-PRG-related signature was developed. Used the median score from the signature, we classified patients in two subgroups. Subsequently, we employed univariate COX, multivariate Cox regression, ROC analysis and constructed a nomogram, Finally, differential analysis, GO and KEGG functional analysis, ESTIMATE algorithm and CIBERSORT algorithm were used to explore the difference between two groups. Results The expression levels of 90.9% pyroptosis-related genes (PRGs) had significant difference compared AML with normal tissues. The results of univariate COX regression analysis demonstrated 10 differentially expressed genes (DEGs) were associated with patients’ OS (p < 0.05). Then, we found OS of patients in the low-risk group was more likely to be lengthened compared with their high-risk counterparts (P < 0.05 both in the TCGA and GEO cohort). After controlling clinical factors, the risk score could still remain an independent predictive element (HR > 1, P < 0.001) of OS in multivariate Cox regression analysis. Furthermore, a nomogram with prognostic value for AML was thus established. Time-dependent ROC analysis proved the predictive power of the signature. Functional analysis suggested that DEGs were mainly concentrated in immune-related pathways, such as humoral immune response and T cell proliferation. TME scores and risk scores were strongly correlated and immune status differed between the risk subgroups. Conclusion A novel PRG-related signature was established to forecast the prognosis in AML, and pyroptosis may be a potential therapeutic target for AML.

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Pyroptosis: A New Regulating Mechanism in Cardiovascular Disease

Cited by 84 publications

References 124 publications

Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis

Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury

Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia

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