The NLRP3 Inflammasome as a Novel Therapeutic Target for Cardiac Fibrosis

Fan, Jiwen; Ren, Meng; Adhikari, Binay Kumar; Wang, Haodong; He, Yuquan

doi:10.2147/jir.s370483

Cited by 9 publications

(7 citation statements)

References 135 publications

(169 reference statements)

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“…177 Prevention of macrophage-inflammasome activation by inhibition of Lp-PLA2 reduces IL-1β secretion and blocks macrophage-mediated myofibroblast transformation. 178,179 Indeed, targeted inflammasome inhibition holds great potential for the treatment of cardiac fibrosis, with its activation occurring in hyperglycemia, hypertension, atrial fibrillation, and MI. 179 Furthermore, targeting other inflammatory and pro-fibrotic factors, such as IL-11, by neutralizing antibodies can reduce cardiac fibrosis.…”

Section: Influencing Microenvironmental Signallingmentioning

confidence: 99%

“…178,179 Indeed, targeted inflammasome inhibition holds great potential for the treatment of cardiac fibrosis, with its activation occurring in hyperglycemia, hypertension, atrial fibrillation, and MI. 179 Furthermore, targeting other inflammatory and pro-fibrotic factors, such as IL-11, by neutralizing antibodies can reduce cardiac fibrosis. 180 Microenvironmental signals originating from ECM also present therapeutic avenues.…”

Section: Influencing Microenvironmental Signallingmentioning

confidence: 99%

“…Furthermore, treatments to increase endothelial angiogenesis, such as milk‐derived EVs, decrease fibrosis levels and increase cardiac function in cardiac hypertrophy 177 . Prevention of macrophage‐inflammasome activation by inhibition of Lp‐PLA2 reduces IL‐1β secretion and blocks macrophage‐mediated myofibroblast transformation 178,179 . Indeed, targeted inflammasome inhibition holds great potential for the treatment of cardiac fibrosis, with its activation occurring in hyperglycemia, hypertension, atrial fibrillation, and MI 179 .…”

Section: Current and Emerging Therapeutic Strategies For Myocardial F...mentioning

confidence: 99%

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Defining cardiac fibrosis complexity and regulation towards therapeutic development

Claridge

Drack

Pinto

et al. 2023

Clinical and Translational Dis

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Cardiac fibrosis is insidious, accelerating cardiovascular diseases, heart failure, and death. With a notable lack of effective therapies, advances in both understanding and targeted treatment of fibrosis are urgently needed. Remodelling of the extracellular matrix alters the biomechanical and biochemical cardiac structure and function, disrupting cell-matrix interactions and exacerbating pathogenesis to ultimately impair cardiac function. Attempts at clinical fibrotic reduction have been fruitless, constrained by an understanding which severely underestimates its dynamic complexity and regulation. Integration of single-cell sequencing and quantitative proteomics has provided new insights into cardiac fibrosis, including reparative or maladaptive processes, spatiotemporal changes and fibroblast heterogeneity. Further studies have revealed microenvironmental and intercellular signalling mechanisms (including soluble mediators and extracellular vesicles), and intracellular regulators including posttranslational/epigenetic modifications, RNA binding proteins, and non-coding RNAs. This understanding of novel disease processes and molecular targets has supported the development of innovative therapeutic strategies. Indeed, targeted modulation of cellular heterogeneity, microenvironmental signalling, and intracellular regulation offer promising pre-clinical therapeutic leads. Clinical development will require further advances in our mechanistic understanding of cardiac fibrosis and dissection of the molecular basis for fibrotic remodelling.This review provides an overview of the complexities of cardiac fibrosis, emerging regulatory mechanisms and therapeutic strategies, and highlights knowledge gaps and opportunities for further investigation towards therapeutic/clinical translation.

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Section: Influencing Microenvironmental Signallingmentioning

confidence: 99%

Section: Influencing Microenvironmental Signallingmentioning

confidence: 99%

Section: Current and Emerging Therapeutic Strategies For Myocardial F...mentioning

confidence: 99%

See 1 more Smart Citation

Defining cardiac fibrosis complexity and regulation towards therapeutic development

Claridge

Drack

Pinto

et al. 2023

Clinical and Translational Dis

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“…It is likely that it is plausible to reduce the extent of ischemic damage in terms of heart attack volume and cerebral oedema and hinder cognitive decay by employing numerous natural compounds such as sinomenine (a kind of alkaloid), paeoniflorin, and resveratrol. However, with little evidence in the literature, further studies on the efficacy and safety of these substances should be conducted [ 113 , 114 ].…”

Section: Nlrp3 Inflammasomementioning

confidence: 99%

Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis

et al. 2022

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Ischemic stroke (also called cerebral ischemia) is one of the leading causes of death and severe disability worldwide. NLR inflammasomes play a crucial role in sensing cell damage in response to a harmful stimuli and modulating the inflammatory response, promoting the release of pro-inflammatory cytokines such as IL-18 and IL-1β following ischemic injury. Therefore, a neuroprotective effect is achieved by inhibiting the expression, assembly, and secretion of inflammasomes, thus limiting the extent of brain detriment and neurological sequelae. This review aims to illustrate the molecular characteristics, expression levels, and assembly of NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin-domain-containing 3) inflammasome, the most studied in the literature, in order to discover promising therapeutic implications. In addition, we provide some information regarding the contribution of NLRP1, NLRP2, and NLRC4 inflammasomes to ischemic stroke pathogenesis, highlighting potential therapeutic strategies that require further study.

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“…Згідно з європейськими рекомендаціями ведення ГКС, 2 години вважаються золотим вікном реваскуляризації. Підтвердженням є те, що в перші 3 години гострої ішемії в міокарді починає значно збільшуватись рівень інфламасом, що провокує майже необоротний процес запалення та посилення подальшого міокардіального пошкодження [14] Результати та їх обговорення. Кількість випадків no-reflow становить 15,3 %, що є одним з найбільших показників, порівнюючи з даними наведених досліджень (STENT-PAMI, POST, та ін.)…”

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Impact of Acute Myocardial Ischemia Duration on Reperfusion Outcomes in STEMI Patients

Salo,

Shpak,

Shumakov

2023

ujcvs

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The aim. To analyze the influence of the duration of acute myocardial ischemia, specifically in ST-elevation myocardial infarction (STEMI) electrocardiographic patterns, on the outcomes of reperfusion interventions. We focused on the assessment of immediate angiographic data in the catheterization laboratory after stenting and investigated whether the frequency of the no-reflow phenomenon is dependent on the time since the onset of anginal pain. Our hypothesis of inferior immediate treatment outcomes is based on the pathophysiological course of ischemic-reperfusion injury in patients with late myocardial infarction. Primarily, this is due to the development of myocardial edema, leading to extravascular compression of the vessel, thereby influencing Thrombolysis in Myocardial Infarction grade 0 blood flow. Materials and methods. We conducted an analysis of 107 angiograms of STEMI patients, who underwent percutaneous coronary intervention at the Amosov National Institute of Cardiovascular Surgery between 2021 and 2023. The patients were categorized into four groups based on the duration of acute myocardial ischemia. The first group included patients with ischemia duration up to two hours, aligning with the golden window for revascularization recommended by the European guidelines. The second, third, and fourth groups consisted of patients with ischemia durations of 3-12 hours, 12-24 hours, and over 48 hours, respectively. Results. Of 104 patients, complete restoration of coronary circulation was achieved in 88 cases, while, unfortunately, 16 patients had TIMI 0/1 blood flow. Such a probability of complication is 15.3% in the studied cohort. According to the clinical profile, the patients were divided into those who had no-reflow (main group) and patients with complete restoration of blood flow (control group). In the group of unrestored blood flow, cardiogenic shock occurred more often, and the infarct-dependent artery was more often occluded than suboccluded. The technique of percutaneous intervention was similar in both groups. Conclusion. The frequency of the no-reflow phenomenon increases with the duration of acute myocardial ischemia. Patients presenting later than 48 hours since the onset of ischemia are more prone to no-reflow (62.5% vs 37.5% if less than 48 hours). Cardiogenic shock is associated with a higher likelihood of the no-reflow phenomenon. The most significant reason for the delay in delivering a STEMI patient to catheterization laboratory anamnestically is the patient’s untimely medical care seeking. In our opinion, this delay can be avoided by increasing awareness about the initial signs of myocardial infarction and the necessity of seeking immediate medical care.

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The NLRP3 Inflammasome as a Novel Therapeutic Target for Cardiac Fibrosis

Cited by 9 publications

References 135 publications

Defining cardiac fibrosis complexity and regulation towards therapeutic development

Defining cardiac fibrosis complexity and regulation towards therapeutic development

Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis

Impact of Acute Myocardial Ischemia Duration on Reperfusion Outcomes in STEMI Patients

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