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An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction.

ABSTRACT: The liver plays a protective role in myocardial infarction (MI). However, very little is known about the mechanisms. Here, we identify mineralocorticoid receptor (MR) as a pivotal nexus that conveys communications between the liver and the heart during MI. Hepatocyte MR deficiency and MR antagonist spironolactone both improve cardiac repair after MI through regulation on hepatic fibroblast growth factor 21 (FGF21), illustrating an MR/FGF21 axis that underlies the liver-to-heart protection against MI. In addition, an upstreaming acute interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway transmits the heart-to-liver signal to suppress MR expression after MI. Hepatocyte Il6 receptor deficiency and Stat3 deficiency both aggravate cardiac injury through their regulation on the MR/FGF21 axis. Therefore, we have unveiled an IL-6/STAT3/MR/FGF21 signaling axis that mediates heart-liver cross-talk during MI. Targeting the signaling axis and the cross-talk could provide new strategies to treat MI and heart failure.

SUBMITTER: Sun JY

PROVIDER: S-EPMC10075967 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction.

Sun Jian-Yong JY Du Lin-Juan LJ Shi Xue-Rui XR Zhang Yu-Yao YY Liu Yuan Y Wang Yong-Li YL Chen Bo-Yan BY Liu Ting T Zhu Hong H Liu Yan Y Ruan Cheng-Chao CC Gan Zhenji Z Ying Hao H Yin Zhinan Z Gao Ping-Jin PJ Yan Xiaoxiang X Li Ruo-Gu RG Duan Sheng-Zhong SZ

Science advances 20230405 14

The liver plays a protective role in myocardial infarction (MI). However, very little is known about the mechanisms. Here, we identify mineralocorticoid receptor (MR) as a pivotal nexus that conveys communications between the liver and the heart during MI. Hepatocyte <i>MR</i> deficiency and MR antagonist spironolactone both improve cardiac repair after MI through regulation on hepatic fibroblast growth factor 21 (FGF21), illustrating an MR/FGF21 axis that underlies the liver-to-heart protection ...[more]

PMID: 37018396

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Project description:Background This study aimed to explore the value of cardiac magnetic resonance tissue tracking (CMR-TT) technology in evaluating heart failure with preserved ejection fraction (HFpEF) in patients with chronic myocardial infarction (CMI). Methods Between June 2016 and March 2022, we included a consecutive series of 92 patients with CMI and 40 healthy controls in this retrospective study. The CMI patients enrolled were divided into different subgroups [HFpEF-CMI group (n=54) and non- heart failure (HF)-CMI group (n=38)] according to the Heart Failure Association (HFA)-PEFF (step 1: P, pre-test assessment; step 2: E, echocardiography and natriuretic peptide score; step 3: F1, functional testing; step 4: F2, final aetiology) diagnostic algorithm. CMR scan was performed at the First Hospital of China Medical University. Quantitative measurements of myocardial damage, such as myocardial strain parameters of both ventricles derived by CMR-TT and infarct size and transmurality by late gadolinium enhancement (LGE), were assessed. One-way analysis of variance, independent samples t-test, and rank sum test were used to compare myocardial impairment among groups. Pearson or Spearman correlation coefficient was used to measure correlations between left ventricular (LV) strains and clinical and functional parameters. Logistic regression analysis and receiver operating characteristic (ROC) curve were performed to identify the best parameter for diagnosing HFpEF-CMI. Results HFpEF-CMI patients demonstrated significantly impaired LV strains and strain rates in all of the three directions (radial, circumferential and longitudinal) compared to non-HF-CMI patients and healthy controls (P<0.001 for all), whereas only global longitudinal strain (GLS) was significantly impaired in HFpEF-CMI patients vs. controls for right ventricular strain parameters (P<0.001). LV strains showed moderate correlation with N-terminal pro-brain natriuretic peptide (radial, circumferential and longitudinal strain, R=−0.401, R=0.408, R=0.407, respectively, P<0.001 for all). LV strains in the three directions (radial, circumferential and longitudinal) [area under ROC curve (AUC) =0.707, 95% confidence interval (CI): 0.603–0.797; AUC =0.708, 95% CI: 0.604–0.798; AUC =0.731, 95% CI: 0.628–0.818; respectively, P<0.01 for all] were discriminators for HFpEF-CMI and non-HF-CMI. LV strains and myocardial infarction volume were independent factors in multi-logistic regression analysis after adjusting for body mass index, age, and sex (P<0.05 for all). Conclusions CMR-TT provides clinicians with useful additional imaging parameters to facilitate the assessment of CMI patients with HFpEF. LV strain parameters can detect early cardiac insufficiency in patients with HFpEF-CMI and have potential value for discriminating between HFpEF and non-HF patients post-CMI.

Dataset Information

An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction.

Publications

An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction.

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