Gasdermin D-mediated pyroptosis in myocardial ischemia and reperfusion injury: Cumulative evidence for future cardioprotective strategies

Acta Pharmaceutica Sinica B, Год журнала: 2022, Номер 13(1), С. 29 - 53

Опубликована: Авг. 14, 2022

Cardiomyocyte death is one of the major mechanisms contributing to development myocardial infarction (MI) and ischemia/reperfusion (MI/R) injury. Due limited regenerative ability cardiomyocytes, understanding cardiomyocyte necessary. Pyroptosis, regulated programmed cell pathways, has recently been shown play important roles in MI MI/R Pyroptosis activated by damage-associated molecular patterns (DAMPs) that are released from damaged cells activate formation an apoptosis-associated speck-like protein containing a CARD (ASC) interacting with NACHT, LRR, PYD domains-containing 3 (NLRP3), resulting caspase-1 cleavage which promotes activation Gasdermin D (GSDMD). This pathway known as canonical pathway. GSDMD also be non-canonical during injury via caspase-4/5/11. Suppression provide cardioprotection against Although effects or on pyroptosis have previously discussed, knowledge concerning these settings remains limited. In this review, evidence vitro, vivo, clinical studies focusing cardiac comprehensively summarized discussed. Implications review will help pave way for new therapeutic target ischemic heart disease.

Язык: Английский

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SIRT3 attenuates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome via autophagy

Biochemical Pharmacology, Год журнала: 2022, Номер 207, С. 115354 - 115354

Опубликована: Ноя. 24, 2022

Язык: Английский

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The role of IFI16 in regulating PANoptosis and implication in heart diseases

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Май 1, 2024

Interferon Gamma Inducible Protein 16 (IFI16) belongs to the HIN-200 protein family and is pivotal in immunological responses. Serving as a DNA sensor, IFI16 identifies viral aberrant DNA, triggering immune inflammatory It implicated diverse cellular death mechanisms, such pyroptosis, apoptosis, necroptosis. Notably, these processes are integral emergent concept of PANoptosis, which encompasses demise pathways. Current research implies significant regulatory role for particularly regarding cardiac pathologies. This review delves into complex interplay between PANoptosis heart diseases, including atherosclerosis, myocardial infarction, failure, diabetic cardiomyopathy. synthesizes evidence IFI16's impact on with intention providing novel insights therapeutic strategies targeting diseases.

Язык: Английский

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Heart Failure With Improved Ejection Fraction: Prevalence, Predictors, and Guideline-Directed Medical Therapy

Cureus, Год журнала: 2024, Номер unknown

Опубликована: Июнь 6, 2024

Recently, a new category of heart failure with improved ejection fraction (HFimpEF) has emerged in the classification system. This is defined as subgroup patients reduced (HFrEF) whose left ventricular recovered partially or completely, no specific cut-off values established yet guidelines. In our review, we aim to provide an overview prevalence, predictors, mechanism remodeling, and management strategies regarding HFimpEF. These constitute sizeable cohort among fraction. Certain patient characteristics including younger age female gender, absence comorbid conditions, low levels biomarkers, non-ischemic etiology were identified positive predictors. The undergoes significant maladaptive changes post leading adverse remodeling influenced duration. Goal-directed medical therapy beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) have notably cardiac function by inducing reverse remodeling. Despite more favorable prognosis compared HFrEF, (EF) still face clinical events quality life, remain at risk outcomes. Although evidence scarce, it advisable continue treatment modalities despite improvement EF, device therapies, prevent relapse deterioration. It imperative conduct further research understand EF amelioration establish guidelines identify direct strategies.

Язык: Английский

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The selective NLRP3 inflammasome inhibitor MCC950 improves isoproterenol-induced cardiac dysfunction by inhibiting cardiomyocyte senescence

European Journal of Pharmacology, Год журнала: 2022, Номер 937, С. 175364 - 175364

Опубликована: Ноя. 3, 2022

Язык: Английский

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Triptolide attenuates cardiac remodeling by inhibiting pyroptosis and EndMT via modulating USP14/Keap1/Nrf2 pathway

Heliyon, Год журнала: 2024, Номер 10(2), С. e24010 - e24010

Опубликована: Янв. 1, 2024

BackgroundCardiac remodeling is a common pathological feature in many cardiac diseases, characterized by hypertrophy and fibrosis. Triptolide (TP) natural compound derived from Tripterygium wilfordii Hook F. However, the related mechanism of it has not been fully understood.Methods resultsTransverse aortic constriction (TAC)-induced hypertrophic mouse model angiotensin II (Ang II)-induced cardiomyocytes were performed. Firstly, results indicate that TP can improve function, decreased cardiomyocyte surface area fibrosis area, as well lowered protein expressions brain natriuretic peptide (BNP), β-major histocompatibility complex (β-MHC), type I III collagen (Col III). Secondly, suppressed pyroptosis, levels Interleukin-1β (IL-1β), Interleukin-18 (IL-18) Enzyme-linked immunosorbent assay (ELISA), pyroptosis-associated proteins. Furthermore, enhanced Nuclear factor erythroid 2-related 2 (Nrf2) Heme oxygenase 1 (HO-1). Interestingly, when Nrf2 was silenced siRNA, lost its properties reducing pyroptosis hypertrophy. In addition, Transforming Growth Factor β1 (TGF-β1)-induced primary human coronary artery endothelial cells (HCAEC) model, found to inhibit process endothelial-to-mesenchymal transition (EndMT), loss endothelial-specific markers gain mesenchymal markers. This accompanied suppression Slug, Snail, Twist expression. Meanwhile, inhibitory effect on EndMT weakened siRNA. Lastly, potential targets identified through network pharmacology analysis, Ubiquitin-Specific Protease 14 (USP14) one them. Simultaneously, data indicated decrease upregulation USP14 Kelch-like ECH-Associated Protein (Keap1) caused remodeling. Keap1 increased silenced. CoIP analysis showed directly interacts with Keap1.ConclusionTP observably reduce targeting USP14/Keap1/Nrf2 pathway, thereby significantly attenuating

Язык: Английский

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Progenitor Cell Function and Cardiovascular Remodelling Induced by SGLT2 Inhibitors

Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(4), С. 145 - 145

Опубликована: Апрель 9, 2024

Sodium-glucose cotransporters 2 (SGLT2) are high-capacity, low-affinity transporters, expressed mainly in the early portion of proximal renal tube, mediating up to 90% glucose uptake, while SGLT1 receptors found small intestine, facilitating absorption. SGLT2 inhibitors (SGLT2i) originally emerged as agents for treatment type diabetes mellitus; however, they soon demonstrated remarkable cardio- and renoprotective actions that led their licensed use heart failure chronic kidney disease, regardless diabetic status. Cardiovascular remodelling represents an umbrella term encompasses changes occur cardiovascular system, from molecular cellular level, tissue organs after local injury, stress, or pressure. SGLT modulation has been shown positively affect many these observed during pathological remodelling. Among different pathophysiological mechanisms contribute adverse remodelling, various stem progenitor cells have be involved, through alterations number function. Recent studies examined effects SGLT2i on cell populations more specifically endothelial (EPCs). Although some no significant effect, others showed can modulate morphology function EPCs. These preliminary observations effect EPCs may responsible beneficial gliflozins and, by extension, disease. The purpose this narrative review is critically discuss recent evidence cardioprotective SGLT2is, context cardiac

Язык: Английский

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Temporal dynamics of PM2.5 induced cell death: Emphasizing inflammation as key mediator in the late stages of prolonged myocardial toxicity

Experimental Cell Research, Год журнала: 2025, Номер 445(1), С. 114423 - 114423

Опубликована: Янв. 14, 2025

Язык: Английский

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Role of METTL14 in cardiomyocyte pyroptosis in mice with heart failure by regulating miR-221-3p RNA methylation

International Immunopharmacology, Год журнала: 2025, Номер 149, С. 114172 - 114172

Опубликована: Фев. 9, 2025

Язык: Английский

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Therapeutic Potential of Gasdermin D‐Mediated Myocardial Pyroptosis in Ischaemic Heart Disease: Expanding the Paradigm From Bench to Clinical Insights

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(3)

Опубликована: Фев. 1, 2025

ABSTRACT Ischaemic heart disease (IHD) remains a leading cause of global morbidity and mortality. One significant contributor to the pathology IHD is excessive release inflammatory mediators during progression. Pyroptosis form programmed cell death (PCD) triggered by activation inflammasomes caspase 1. The 1 proteolytically cleaves gasdermin D (GSDMD) activated amino acid terminus (GSDMD‐NT), disruption plasma membrane. This cascade events considered canonical pathway pyroptosis. also caused oxidative stress, thereby triggering noncanonical pyroptosis via caspases 4/5/11. Previous studies have provided compelling evidence close relationship between aetiology (e.g., acute myocardial infarction, ischaemia reperfusion injury chronic infarction), as well association with unfavourable clinical outcomes. Several interventions aimed at targeting demonstrated promising therapeutic benefits against IHD‐related pathologies. review provides mechanistic insights into roles in from vitro, vivo perspectives. In‐depth understanding this area could pave way for future development novel strategies IHD.

Язык: Английский

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