Inhibition of the NLRP3/IL‐1β axis protects against sepsis‐induced cardiomyopathy

Background Septic cardiomyopathy worsens the prognosis of critically ill patients. Clinical data suggest that interleukin‐1β (IL‐1β), activated by the NLRP3 inflammasome, compromises cardiac function. Whether or not deleting Nlrp3 would prevent cardiac atrophy and improve diastolic cardiac function...

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Published in:Journal of cachexia, sarcopenia and muscle sarcopenia and muscle, 2021-12, Vol.12 (6), p.1653-1668
Main Authors: Busch, Katharina, Kny, Melanie, Huang, Nora, Klassert, Tilman E., Stock, Magdalena, Hahn, Alexander, Graeger, Sebastian, Todiras, Mihail, Schmidt, Sibylle, Chamling, Bishwas, Willenbrock, Michael, Groß, Stefan, Biedenweg, Doreen, Heuser, Arnd, Scheidereit, Claus, Butter, Christian, Felix, Stephan B., Otto, Oliver, Luft, Friedrich C., Slevogt, Hortense, Fielitz, Jens
Format: Article
Language:English
Subjects:
Animals
Cardiac function
Cardiomyocytes
Cardiomyopathies - etiology
Cardiomyopathy
Flow velocity
Heart
Heart failure
Humans
Inflammasomes
Interleukin-1beta
Interleukin‐1 beta
Investigations
Ischemia
Kinases
Laboratory animals
Male
Mechanical properties
Metabolism
Mice
Musculoskeletal system
NLR Family, Pyrin Domain-Containing 3 Protein - genetics
NLR family, pyrin domain‐containing 3 protein
Original
Rats
Sepsis
Sepsis - complications
Surgery
Tumor necrosis factor-TNF
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Summary:Background Septic cardiomyopathy worsens the prognosis of critically ill patients. Clinical data suggest that interleukin‐1β (IL‐1β), activated by the NLRP3 inflammasome, compromises cardiac function. Whether or not deleting Nlrp3 would prevent cardiac atrophy and improve diastolic cardiac function in sepsis was unclear. Here, we investigated the role of NLRP3/IL‐1β in sepsis‐induced cardiomyopathy and cardiac atrophy. Methods Male Nlrp3 knockout (KO) and wild‐type (WT) mice were exposed to polymicrobial sepsis by caecal ligation and puncture (CLP) surgery (KO, n = 27; WT, n = 33) to induce septic cardiomyopathy. Sham‐treated mice served as controls (KO, n = 11; WT, n = 16). Heart weights and morphology, echocardiography and analyses of gene and protein expression were used to evaluate septic cardiomyopathy and cardiac atrophy. IL‐1β effects on primary and immortalized cardiomyocytes were investigated by morphological and molecular analyses. IonOptix and real‐time deformability cytometry (RT‐DC) analysis were used to investigate functional and mechanical effects of IL‐1β on cardiomyocytes. Results Heart morphology and echocardiography revealed preserved systolic (stroke volume: WT sham vs. WT CLP: 33.1 ± 7.2 μL vs. 24.6 ± 8.7 μL, P 
ISSN:2190-5991
2190-6009
DOI:10.1002/jcsm.12763