Multiorgan characterization of inflammasome component expression in a rat model of advanced heart failure

IF 3.7 2区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

ESC Heart Failure Pub Date : 2025-08-11 DOI:10.1002/ehf2.15362

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

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引用次数: 0

Abstract

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.

Abstract Image

查看原文本刊更多论文

晚期心力衰竭大鼠模型中炎性体成分表达的多器官特征。

目的：针对心衰（HF）的炎症小体可能是一种新的治疗选择。然而，以往的研究只关注心肌炎性体的改变，关于它们在hf相关的多器官功能障碍中的调节和作用的数据很少。因此，我们旨在测定晚期心衰大鼠模型中各种炎性体成分的心肌、肺、肝和肾表达。方法与结果：大鼠行主动脉横缩术（TAC），随访15周。有2 - 3个晚期HF临床体征的动物被纳入TAC-HF组（n = 6）。同时观察轻度HF TAC大鼠（0-1体征，TAC- m组，n = 6）。6只假手术的动物作为对照。采用Western blot法检测左心室（LV）、右心室（RV）、肺、肝、肾组织中炎性小体成分蛋白的表达。尽管TAC- hf组和TAC- m组的临床状态存在差异，但所有TAC动物都出现了严重的心功能障碍和心肌重构。在黑色素瘤2 （AIM2）和NLR家族CARD结构域蛋白4 （NLRC4）中缺失的炎症小体传感器在TAC-HF组的左室和右室中与sham相比均上调。TAC-HF动物肺组织中AIM2和NLR家族pyrin domain containing protein 3 （NLRP3）表达升高，NLRC4表达不升高。两组患者均出现肺充血和cd68阳性白细胞浸润。尽管存在肾萎缩和纤维化，但在TAC-HF组，肝脏中的炎性体成分下调，肾脏中的炎性体成分保持不变。炎性体的改变在TAC-M动物中基本不存在。结论：炎性小体在晚期心衰患者的特定器官中表现出不同的表达模式。未来旨在对抗心衰炎症的研究应考虑到这些发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESC Heart Failure Medicine-Cardiology and Cardiovascular Medicine

CiteScore

7.00

自引率

7.90%

发文量

461

审稿时长

12 weeks

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.