NLRP3 inflammasome involves in the pathophysiology of sepsis-induced myocardial dysfunction by multiple mechanisms

Zhang, Hongwei; Liao, Jian; Jin, Litong; Lin, Yan

doi:10.1016/j.biopha.2023.115497

Cited by 5 publications

(3 citation statements)

References 118 publications

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“…38 In fact, aberrant activation of NLRP3 is implicated in the pathogenesis of SIMD, and this molecule has been identified as an upstream protein that triggers early-stage myocardial injury. 39,40 Previous studies have demonstrated that NLRP3 expression is upregulated in the myocardium of patients with viral myocarditis and myocardial infarction, and further verification has shown that activation of NLRP3 contributes to the progression of these cardiac disorders. 36,41,42 In addition, the intrinsic links between NLRP3 and pyroptosis have been comprehensively investigated.…”

Section: Discussionmentioning

confidence: 99%

The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice

Wang,

Tang

et al. 2024

Journal of Cardiovascular Pharmacology

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Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. The current study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing (RNA-seq) demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NLRP3 upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for SIMD therapy.

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Section: Discussionmentioning

confidence: 99%

The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice

Wang,

Tang

et al. 2024

Journal of Cardiovascular Pharmacology

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“…Furthermore, irisin has been shown to favor the anti-inflammatory M2-type macrophage polarization over the inflammatory M1-type through activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ)-related anti-inflammatory system and the nuclear factor-erythroid 2-related factor 2 (Nrf2)-related antioxidant genes [ 22 ]. Finally, irisin prevents the formation of inflammasome, thus, ameliorating the inflammatory response and promoting cellular viability [ 29 , 33 , 47 ] ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent experimental studies have demonstrated a protective role of irisin in sepsis-induced organ dysfunction through the inhibition of multiple inflammatory pathways [ 21 , 28 , 29 , 30 , 31 , 32 , 33 ]. However, irisin has not been thoroughly studied in humans, i.e., in patients with sepsis and septic shock.…”

Section: Introductionmentioning

confidence: 99%

Alterations of the Adipo–Myokine Irisin in Sepsis and Septic Shock: Diagnostic and Prognostic Implications

Karampela,

Vallianou,

Tsilingiris

et al. 2024

Biomolecules

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Irisin, a novel adipo-myokine with metabolic regulatory functions, exerts anti-inflammatory, antioxidant, and anti-apoptotic actions that may confer protection against sepsis-induced organ injury in experimental studies. Until now, only one human study has explored circulating irisin at sepsis onset. We aimed to examine serum irisin and its kinetics in critically ill patients with sepsis and septic shock with regard to sepsis severity and outcome. We enrolled 102 critically ill patients with sepsis or septic shock within 48 h of diagnosis and 102 age- and gender-matched healthy controls. Irisin was determined in serum upon enrollment in all participants and one week later in patients using an immunoenzymatic method. The outcome of sepsis was recorded 28 days after enrollment. At enrollment, circulating irisin was significantly lower in patients than controls (22.3 ± 6.8 μg/L vs. 28.1 ± 6.7 μg/L, p < 0.001), and increased significantly one week later (22.3 ± 6.8 μg/L vs. 26.6 ± 9.5 μg/L, p < 0.001). Irisin was significantly lower in patients who presented with septic shock than those with sepsis, and in non-survivors than survivors both at enrollment and one week later. However, kinetics of irisin did not differ between the groups (p > 0.05). Patients with higher circulating irisin during the first week of sepsis had a better outcome (p < 0.001). Lower irisin was independently associated with 28-day mortality (sepsis onset: HR 0.44, 95% C.I. 0.26–0.77, p = 0.004 and one week after: HR 0.37, 95% C.I. 0.23–0.58, p < 0.001). Irisin was negatively correlated with severity scores, metabolic, and inflammatory biomarkers. Circulating irisin decreases early in sepsis and is an independent predictor of 28-day mortality. Irisin may be a promising diagnostic and prognostic sepsis biomarker; nevertheless, larger studies are needed to explore its role in sepsis.

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Molecular inflammopharmacology and therapeutics

Kumar,

Harilal

2024

Biochemical and Molecular Pharmacology in Drug Discovery

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NLRP3 inflammasome involves in the pathophysiology of sepsis-induced myocardial dysfunction by multiple mechanisms

Cited by 5 publications

References 118 publications

The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice

The protective effects of ruscogenin against lipopolysaccharide-induced myocardial injury in septic mice

Alterations of the Adipo–Myokine Irisin in Sepsis and Septic Shock: Diagnostic and Prognostic Implications

Molecular inflammopharmacology and therapeutics

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