NLRP3 inflammasome activation during myocardial ischemia reperfusion is cardioprotective

Sandanger, Øystein; Gao, Erhe; Ranheim, Trine; Bliksøen, Marte; Kaasboll, OJ; Alfsnes, Kristian; Nymo, Ståle H.; Rashidi, Azita; Ohm, Ingrid Kristine; Attramadal, Håvard; Aukrust, Pål; Vinge, Leif Erik; Yndestad, Arne

doi:10.1016/j.bbrc.2015.12.051

Cited by 85 publications

(65 citation statements)

References 32 publications

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“…Very recently, a role for NLRP3 inflammasome activation in the modulation of the Reperfusion Injury Salvage Kinase (RISK) pathway has been suggested [20]. Thus, we quantified expression and activity (in terms of phosphorylation) of the key members of this pathway.…”

Section: Resultsmentioning

confidence: 99%

“…Few studies demonstrated that the depletion of even one of the inflammasome complex components, either the sensor (NLRP3) or the effector enzyme (caspase-1), can prevent its activation and protect the heart preventing ischemic injury and adverse cardiac remodelling [22–24]. In contrast, Sandanger et al [20] showed that absence of NLRP3 results in increased myocardial infarct size after in vivo IR, whereas Jong et al [14] concluded that NLRP3 plays no role in acute myocardial infarction due to low cardiac expression. As stated by the same authors, significant differences in the used methodologies as well as in the specific endpoint of interest may help to explain this inconsistency [25].…”

Section: Discussionmentioning

confidence: 99%

“…Very recently, a role for NLRP3 inflammasome activation in the cardioprotective RISK pathway has been faintly suggested, but not convincingly demonstrated [20]. Here we measured the entire RISK pathway, which includes Akt and ERK1/2 activation and GSK3 β inhibition through phosphorylation [30].…”

Section: Discussionmentioning

confidence: 99%

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Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways

Mastrocola

Penna

Tullio

et al. 2016

Oxidative Medicine and Cellular Longevity

114

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Although the nucleotide-binding oligomerization domain- (NOD-) like receptor pyrin domain containing 3 (NLRP3) inflammasome has been recently detected in the heart, its role in cardiac ischemia/reperfusion (IR) is still controversial. Here, we investigate whether a pharmacological modulation of NLRP3 inflammasome exerted protective effects in an ex vivo model of IR injury. Isolated hearts from male Wistar rats (5-6 months old) underwent ischemia (30 min) followed by reperfusion (20 or 60 min) with and without pretreatment with the recently synthetized NLRP3 inflammasome inhibitor INF4E (50 μM, 20 min before ischemia). INF4E exerted protection against myocardial IR, shown by a significant reduction in infarct size and lactate dehydrogenase release and improvement in postischemic left ventricular pressure. The formation of the NLRP3 inflammasome complex was induced by myocardial IR and attenuated by INF4E in a time-dependent way. Interestingly, the hearts of the INF4E-pretreated animals displayed a marked improvement of the protective RISK pathway and this effect was associated increase in expression of markers of mitochondrial oxidative phosphorylation. Our results demonstrate for the first time that INF4E protected against the IR-induced myocardial injury and dysfunction, by a mechanism that involves inhibition of the NLRP3 inflammasome, resulting in the activation of the prosurvival RISK pathway and improvement in mitochondrial function.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways

Mastrocola

Penna

Tullio

et al. 2016

Oxidative Medicine and Cellular Longevity

114

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“…reported that genetic deletion of NLRP3 gene protects animal heart from challenges including I/R 6, while Sandanger et al . showed that the NLRP3 inflammasome activation during myocardial I/R is cardioprotective 37. Future studies are warranted to clarify this issue.…”

Section: Discussionmentioning

confidence: 93%

Naoxintong attenuates Ischaemia/reperfusion Injury through inhibiting NLRP3 inflammasome activation

Wang

Yan

et al. 2016

J Cellular Molecular Medi

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Naoxintong (NXT) is a Chinese Materia Medica standardized product extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinensis, Astragali Radix. Naoxintong is clinically effective in treating ischaemia heart disease. Nucleotide‐binding oligomerization domain‐Like Receptor with a Pyrin domain 3 (NLRP3) inflammasome has been critically involved in myocardial ischaemia/reperfusion (I/R) injury. Here, we have been suggested that NXT might attenuate myocardial I/R injury via suppression of NLRP3 inflammasome activation. Male C57BL6 mice were subjected to myocardial I/R injury via 45 min. coronary ligation and release for the indicated times. Naoxintong (0.7 g/kg/day) and PBS were orally administrated for 2 weeks before surgery. Cardiac function assessed by echocardiography was significantly improved in the NXT group compared to PBS group at day 2 after myocardial I/R. NLRP3 inflammasome activation is crucially involved in the initial inflammatory response after myocardial I/R injury, leading to cleaved caspase‐1, mature interleukin (IL)‐1β production, accompanying by macrophage and neutrophil infiltration. The cardioprotective effect of NXT was associated with a diminished NLRP3 inflammasome activation, decreased pro‐inflammatory macrophage (M1 macrophages) and neutrophil infiltration after myocardial I/R injury. In addition, serum levels of IL‐1β, indicators of NLRP3 inflammasome activation, were also significantly suppressed in the NXT treated group after I/R injury. Naoxintong exerts cardioprotive effects at least partly by suppression of NLRP3 inflammasome activation in this I/R injury model.

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“…Investigations into the role of the NLRP3 inflammasome in ischaemic injury have yielded mixed findings, with some studies reporting increased resistance to infarction in hearts in which NLRP3 inflammasome has been genetically deleted 175,176 , and others reporting neutral findings 177,178 . Importantly, the NLRP3 inflammasome is not the only activator of caspase 1; at least three other similar inflammasome systems that activate caspase 1 have been described 179 , which might explain why chronic deletion of the NLRP3 inflammasome might be compensated for by activation of another inflammasome.…”

Section: Pyroptosis and The Innate Immune Systemmentioning

confidence: 99%

New and revisited approaches to preserving the reperfused myocardium

et al. 2017

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Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling.

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NLRP3 inflammasome activation during myocardial ischemia reperfusion is cardioprotective

Cited by 85 publications

References 32 publications

Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways

Pharmacological Inhibition of NLRP3 Inflammasome Attenuates Myocardial Ischemia/Reperfusion Injury by Activation of RISK and Mitochondrial Pathways

Naoxintong attenuates Ischaemia/reperfusion Injury through inhibiting NLRP3 inflammasome activation

New and revisited approaches to preserving the reperfused myocardium

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