NLRP3 Inflammasome Activation Through Heart-Brain Interaction Initiates Cardiac Inflammation and Hypertrophy During Pressure Overload

Higashikuni, Yasutomi; Liu, Wenhao; Numata, Genri; Tanaka, Kimie; Fukuda, Daiju; Tanaka, Yu; Hirata, Yoichiro; Imamura, Teruhiko; Takimoto, Eiki; Komuro, Issei; Sata, Masataka

doi:10.1161/circulationaha.122.060860

Cited by 80 publications

(35 citation statements)

References 53 publications

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“…GSDMD is a gasdermin family sharing the pore‐forming domains. Despite the necessity of the inflammasome activation in protecting against infections, the system results in unnecessary inflammatory diseases by inflammasome overactivation 27–29 …”

Section: Components and Modulation Of The Panoptosome Complexesmentioning

confidence: 99%

PANoptosis: Mechanisms, biology, and role in disease

Sun,

Yang,

Meng

et al. 2023

Immunological Reviews

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SummaryCell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell death modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which can be mediated by multifaceted PANoptosome complexes assembled via integrating components from other cell death modalities. There is growing interest in the process and function of PANoptosis. Accumulating evidence suggests that PANoptosis occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, and cancer. Given the impact of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and PANoptosis activation, and outlines the multifaceted roles of PANoptosis in diseases together with a potential for therapeutic targeting. We also discuss important concepts and pressing issues for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is crucial for identifying novel therapeutic targets and strategies.

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Section: Components and Modulation Of The Panoptosome Complexesmentioning

confidence: 99%

PANoptosis: Mechanisms, biology, and role in disease

Sun,

Yang,

Meng

et al. 2023

Immunological Reviews

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“…Inflammation plays an important role in the development of CVDs. The most current research focused on the NLRP3 inflammasome [77,78] , and other inflammasomes were poorly studied [79] (Table 2).…”

Section: Inflammasomes In Cardiovascular Diseasesmentioning

confidence: 99%

Inflammation macrophages contribute to cardiac homeostasis

Wang

et al. 2023

Cardiology Plus

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Cardiovascular diseases (CVDs) have high morbidity. Many endogenous and exogenous factors provoke the innate immune response causing tissue damage and accelerating the progression of the diseases. The macrophages are the major cells mediating the inflammatory response. Inflammasomes are multi-protein complexes that recognize danger signals, activate cytokines, and participate in the inflammatory response. Both macrophages and inflammasomes play a critical role in the development and progression of CVDs, such as myocardial infarction, hypertension, and atherosclerosis. This review will summarize the studies on macrophages and inflammasomes and discuss potential therapeutic interventions. Moreover, macrophages and inflammasomes play distinct role in the inflammation process, but closely linked. The inflammasome system occur in macrophages, and macrophage pyroptosis may be provoked by inflammasome activation. The cytokines secreted by macrophages may be related to the activation of inflammasomes, and further activate macrophages in the heart and cause the interconversion of M1 phenotype and M2 phenotype. The mechanism of inflammasomes regulating macrophage polarization remains to be further investigated.

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“…Similarly, a recent study, based on NLRP3 gene deletion in male C57Bl/6J mice, revealed that prevention of the early compensatory cardiac hypertrophy response post-TAC accelerated LV dilation and aggravated cardiac dysfunction. 8 Thus, the potential of IL-1β as a therapeutic target to limit HF development in non-ischemic cardiomyopathy currently remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Blocking Interleukin-1β transiently limits left ventricular dilation and modulates cardiac lymphangiogenesis in a mouse pressure-overload model

Heron

Lemarcis

Laguerre

et al. 2023

Preprint

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Blocking inflammatory pathways, such as the inflammasome or IL-1β, is a promising therapeutic target in both ischemic and non-ischemic heart failure (HF). We hypothesize that IL-1β may stimulate cardiac lymphangiogenesis, driven by left ventricular dilation in HF. Thus, blocking IL-1β signaling may reduce lymphangiogenesis, which could delay resolution of myocardial edema and inflammation, aggravate cardiac fibrosis, and accelerate HF development. Here, we investigated the effects of early versus late anti-IL-1β treatment during pressure-overload induced by transaortic constriction (TAC) in Balb/c mice prone to left ventricular (LV) dilation. We also investigated links between perivascular lymphatics and fibrosis in ischemic versus dilated cardiomyopathy (DCM) HF patients. We found that early treatment transiently delayed LV dilation, but did not alter cardiac hypertrophy or dysfunction at 8 weeks post-TAC. Late treatment reduced cardiac lymphangiogenesis and lymphatic CCL21 gradients. Surprisingly, cardiac inflammation, fibrosis and dysfunction were not aggravated despite reduced lymphatic density. Further, similar as in mice, increased perivascular lymphatic density in HF patients was associated with less perivascular fibrosis. In conclusion, we found limited functional cardiac benefit of IL-1β blockage when initiated before onset of lymphangiogenesis post-TAC in Balb/c mice. In contrast, late treatment reduced cardiac lymphangiogenesis. HF onset was however not significantly accelerated, likely reflecting lymphatic transport dysfunction post-TAC. Taken together, the therapeutic window for anti-IL-1β treatment appears crucial, as initiation of treatment during the lymphangiogenic response, induced by LV dilation, may limit the potential cardiac benefit in HF patients. Further, our data indicate that IL-1β-independent perivascular lymphangiogenesis may limit perivascular fibrosis.

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NLRP3 Inflammasome Activation Through Heart-Brain Interaction Initiates Cardiac Inflammation and Hypertrophy During Pressure Overload

Cited by 80 publications

References 53 publications

PANoptosis: Mechanisms, biology, and role in disease

PANoptosis: Mechanisms, biology, and role in disease

Inflammation macrophages contribute to cardiac homeostasis

Blocking Interleukin-1β transiently limits left ventricular dilation and modulates cardiac lymphangiogenesis in a mouse pressure-overload model

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