Therapeutic implications of targeting pyroptosis in Cardiac-related etiology of heart failure

Habimana, Olive; Salami, Oluwabukunmi Modupe; Peng, Jin-Fu; Yi, Guanghui

doi:10.1016/j.bcp.2022.115235

Cited by 8 publications

(7 citation statements)

References 151 publications

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“… 34 Pyroptosis is a dominant cell death process in cardiomyocytes, immune cells, endothelial cells, and cardiac fibroblasts and participates in the pathogenesis of cardiac diseases that contribute to heart failure. 35 Sinusoidal liver endothelial cells contribute to liver fibrosis through inflammasome activation and pyroptosis. 36 Our results showed that heme-induced endothelial cell pyroptosis occurred through the NLRP3/GSDMD axis, and GSDMD deletion suppressed the effects of heme on SIRS in mice.…”

Section: Discussionmentioning

confidence: 99%

Heme-Inducing Endothelial Pyroptosis Plays a Key Role in Radiofrequency Ablation of Hepatic Hemangioma Leading to Systemic Inflammatory Response Syndrome

Yao,

Kong,

et al. 2024

JIR

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Purpose Systemic inflammatory response syndrome (SIRS) is a common complication of radiofrequency ablation (RFA) for hepatic hemangiomas. RFA can cause hemolytic reactions during hepatic hemangioma ablation. However, the mechanisms underlying RFA-induced SIRS remain unclear. Methods We established an orthotopic liver hemangioma model and performed radiofrequency ablation. The levels of interleukin (IL)-1β and IL-18 and the production of ROS were measured. The wet-to-dry lung ratio, inflammation score, and in vivo endothelial cell permeability were examined. GSDMD −/− mice were used to investigate the effect of heme-inducing SIRS. RNA sequencing (RNA-seq) was performed to identify the main pathways underlying heme-induced SIRS. Western blotting and immunoprecipitation were used to determine the changes and interactions of associated proteins. Results The levels of heme, IL-1β, and IL-18 were significantly increased after RFA. The wet-to-dry lung ratio increased in hepatic hemangiomas after RFA, indicating that SIRS occurred. Heme induced increased levels of IL-1β and IL-18, cell death, wet-to-dry lung radio, and inflammation score in vitro and in vivo, indicating that heme induced SIRS and pyroptosis. Furthermore, GSDMD participates in heme-induced SIRS in mice, and GSDMD deletion in mice reverses the effect of heme. Heme regulates NLRP3 activation through the NOX4/ROS/TXNIP-TRX pathway, and an N-acetyl-L-cysteine (NAC) or NOX4 inhibitor (GLX351322) reverses heme-induced SIRS. Conclusion Our findings suggest that heme induces endothelial cell pyroptosis and SIRS in mice and decreasing heme levels and ROS scavengers may prevent SIRS in hepatic hemangioma after RFA.

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Section: Discussionmentioning

confidence: 99%

Heme-Inducing Endothelial Pyroptosis Plays a Key Role in Radiofrequency Ablation of Hepatic Hemangioma Leading to Systemic Inflammatory Response Syndrome

Yao,

Kong,

et al. 2024

JIR

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“…The interaction between inflammasome and pyroptosis is emerging as two critical pathophysiological mechanisms contributing to the development of heart failure (HF). 28 While the occurrence of inflammasome-mediated pyroptosis has been observed in various tissues and cell types, additional evidence is necessary to establish its definitive role in the progression and underlying mechanisms of certain heart diseases. 29 Epidemiological studies have highlighted obesity, hypertension, and aging as key risk factors for HF, thus intensifying research efforts to investigate the crucial pathological involvement of inflammasome and pyroptosis in the pathogenesis of HF.…”

Section: Discussionmentioning

confidence: 99%

The role of the inflammasome and pyroptosis in heart failure

Li,

Ye,

Yang

et al. 2023

Eur J Inflamm

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Heart failure (HF) is a complicated clinical syndrome caused by abnormal cardiac structure and/or function, leading to ventricular filling and/or ejection dysfunction. Pyroptosis is a newly identified form of programmed cell death often accompanied by inflammation during HF. The NLRP3 inflammasome, acting as a caspase-1 activation platform, plays a critical role in the production of key pro-inflammatory cytokines and pyroptosis. Therefore, cell death and inflammasomes are involved in the pathophysiological process of HF. Our paper will review the latest research progress on the relationship among pyroptosis, inflammasomes, and HF.

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“… 167 Pyroptosis occurs primarily in cardiac fibroblasts, and the reduced number of cardiomyocytes induced by pyroptosis is a key mediator leading to HF. 168 Ferroptosis plays an important role in HF due to myocardial infarction. Ferroptosis has regulatory mechanisms for the formation of many ferroptosis regulators.…”

Section: Cardiovascular Diseasementioning

confidence: 99%

Endoplasmic reticulum stress-mediated cell death in cardiovascular disease

An,

Wang,

Guan

et al. 2024

Cell Stress and Chaperones

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Therapeutic implications of targeting pyroptosis in Cardiac-related etiology of heart failure

Cited by 8 publications

References 151 publications

Heme-Inducing Endothelial Pyroptosis Plays a Key Role in Radiofrequency Ablation of Hepatic Hemangioma Leading to Systemic Inflammatory Response Syndrome

Heme-Inducing Endothelial Pyroptosis Plays a Key Role in Radiofrequency Ablation of Hepatic Hemangioma Leading to Systemic Inflammatory Response Syndrome

The role of the inflammasome and pyroptosis in heart failure

Endoplasmic reticulum stress-mediated cell death in cardiovascular disease

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