Dávid Nagy, Zsófia Onódi, Márton Kocsis, Artúr Tóth, Tímea Bálint, Attila Oláh, Alex Ali Sayour, Bálint András Barta, Béla Merkely, Péter Ferdinandy, Tamás Radovits, Zoltán V. Varga, Mihály Ruppert
{"title":"晚期心力衰竭大鼠模型中炎性体成分表达的多器官特征。","authors":"Dávid Nagy, Zsófia Onódi, Márton Kocsis, Artúr Tóth, Tímea Bálint, Attila Oláh, Alex Ali Sayour, Bálint András Barta, Béla Merkely, Péter Ferdinandy, Tamás Radovits, Zoltán V. Varga, Mihály Ruppert","doi":"10.1002/ehf2.15362","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>Targeting inflammasomes in heart failure (HF) might represent a novel therapeutic option. Nevertheless, previous studies focused only on myocardial inflammasome alterations, and data are scarce regarding their regulation and role in HF-associated multiorgan dysfunction. Therefore, we aimed to determine the myocardial, pulmonary, hepatic and renal expression of various inflammasome components in a rat model of advanced HF.</p>\n </section>\n \n <section>\n \n <h3> Methods and results</h3>\n \n <p>Rats underwent transverse aortic constriction (TAC) and were followed-up for 15 weeks. Animals featuring two to three clinical signs of advanced HF were included in the TAC-HF group (<i>n</i> = 6). TAC rats with mild HF were also investigated (0–1 signs, TAC-M group, <i>n</i> = 6). Six sham-operated animals served as controls. The expressions of inflammasome component proteins in left ventricle (LV), right ventricle (RV), lung, liver and kidney tissue were measured with Western blot. Despite the differences between the clinical state of the TAC-HF and TAC-M groups, severe cardiac dysfunction and myocardial remodelling developed in all TAC animals. Absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasome sensors were up-regulated in both the LV and RV of the TAC-HF group compared with sham. AIM2 and NLR family pyrin domain-containing protein 3 (NLRP3), but not NLRC4 expression were elevated in the lungs of the TAC-HF animals. Additionally, pulmonary congestion and CD68-positive leukocyte infiltration were observed in both TAC groups. Inflammasome components were down-regulated in the liver and remained unchanged in the kidneys of the TAC-HF group, despite the presence of renal atrophy and fibrosis. Inflammasome changes were predominantly absent in TAC-M animals.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Inflammasome expression shows distinct patterns in specific organs in advanced HF. Future studies aiming to antagonize inflammation in HF should take these findings into consideration.</p>\n </section>\n </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3601-3613"},"PeriodicalIF":3.7000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15362","citationCount":"0","resultStr":"{\"title\":\"Multiorgan characterization of inflammasome component expression in a rat model of advanced heart failure\",\"authors\":\"Dávid Nagy, Zsófia Onódi, Márton Kocsis, Artúr Tóth, Tímea Bálint, Attila Oláh, Alex Ali Sayour, Bálint András Barta, Béla Merkely, Péter Ferdinandy, Tamás Radovits, Zoltán V. Varga, Mihály Ruppert\",\"doi\":\"10.1002/ehf2.15362\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>Targeting inflammasomes in heart failure (HF) might represent a novel therapeutic option. Nevertheless, previous studies focused only on myocardial inflammasome alterations, and data are scarce regarding their regulation and role in HF-associated multiorgan dysfunction. Therefore, we aimed to determine the myocardial, pulmonary, hepatic and renal expression of various inflammasome components in a rat model of advanced HF.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods and results</h3>\\n \\n <p>Rats underwent transverse aortic constriction (TAC) and were followed-up for 15 weeks. Animals featuring two to three clinical signs of advanced HF were included in the TAC-HF group (<i>n</i> = 6). TAC rats with mild HF were also investigated (0–1 signs, TAC-M group, <i>n</i> = 6). Six sham-operated animals served as controls. The expressions of inflammasome component proteins in left ventricle (LV), right ventricle (RV), lung, liver and kidney tissue were measured with Western blot. Despite the differences between the clinical state of the TAC-HF and TAC-M groups, severe cardiac dysfunction and myocardial remodelling developed in all TAC animals. Absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasome sensors were up-regulated in both the LV and RV of the TAC-HF group compared with sham. AIM2 and NLR family pyrin domain-containing protein 3 (NLRP3), but not NLRC4 expression were elevated in the lungs of the TAC-HF animals. Additionally, pulmonary congestion and CD68-positive leukocyte infiltration were observed in both TAC groups. Inflammasome components were down-regulated in the liver and remained unchanged in the kidneys of the TAC-HF group, despite the presence of renal atrophy and fibrosis. 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Multiorgan characterization of inflammasome component expression in a rat model of advanced heart failure
Aims
Targeting inflammasomes in heart failure (HF) might represent a novel therapeutic option. Nevertheless, previous studies focused only on myocardial inflammasome alterations, and data are scarce regarding their regulation and role in HF-associated multiorgan dysfunction. Therefore, we aimed to determine the myocardial, pulmonary, hepatic and renal expression of various inflammasome components in a rat model of advanced HF.
Methods and results
Rats underwent transverse aortic constriction (TAC) and were followed-up for 15 weeks. Animals featuring two to three clinical signs of advanced HF were included in the TAC-HF group (n = 6). TAC rats with mild HF were also investigated (0–1 signs, TAC-M group, n = 6). Six sham-operated animals served as controls. The expressions of inflammasome component proteins in left ventricle (LV), right ventricle (RV), lung, liver and kidney tissue were measured with Western blot. Despite the differences between the clinical state of the TAC-HF and TAC-M groups, severe cardiac dysfunction and myocardial remodelling developed in all TAC animals. Absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasome sensors were up-regulated in both the LV and RV of the TAC-HF group compared with sham. AIM2 and NLR family pyrin domain-containing protein 3 (NLRP3), but not NLRC4 expression were elevated in the lungs of the TAC-HF animals. Additionally, pulmonary congestion and CD68-positive leukocyte infiltration were observed in both TAC groups. Inflammasome components were down-regulated in the liver and remained unchanged in the kidneys of the TAC-HF group, despite the presence of renal atrophy and fibrosis. Inflammasome changes were predominantly absent in TAC-M animals.
Conclusions
Inflammasome expression shows distinct patterns in specific organs in advanced HF. Future studies aiming to antagonize inflammation in HF should take these findings into consideration.
期刊介绍：
ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.
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