FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus

Abstract Background The study aimed to investigate an association of increased liver fibrosis with acute myocardial infarction (AMI), and to investigate the mediating effect of serum follistatin-like protein 3 (FSTL3) on the association in patients with type 2 diabetes mellitus (T2DM). Method A tota...

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Main Authors: Wenfei Duan, Ruixiao Shi, Fang Yang, Zhoujunhao Zhou, Lihong Wang, Zhe Huang, Shufei Zang
Format: Article
Language:English
Published: BMC 2023-10-01
Series:Cardiovascular Diabetology
Subjects:
Online Access:https://doi.org/10.1186/s12933-023-02024-x
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author Wenfei Duan
Ruixiao Shi
Fang Yang
Zhoujunhao Zhou
Lihong Wang
Zhe Huang
Shufei Zang
author_facet Wenfei Duan
Ruixiao Shi
Fang Yang
Zhoujunhao Zhou
Lihong Wang
Zhe Huang
Shufei Zang
author_sort Wenfei Duan
collection DOAJ
description Abstract Background The study aimed to investigate an association of increased liver fibrosis with acute myocardial infarction (AMI), and to investigate the mediating effect of serum follistatin-like protein 3 (FSTL3) on the association in patients with type 2 diabetes mellitus (T2DM). Method A total of 1424 participants were included in this study, and were firstly divided into two groups: 429 T2DM patients and 995 T2DM patients with NAFLD to assess the association of NAFLD and AMI. Then 995 T2DM co-existent NAFLD patients were categorized by NAFLD fibrosis risk to explore the association between NAFLD fibrosis risk and AMI. Immunohistochemistry staining and semi-quantitative analysis of liver FSTL3 were performed in 60 patients with NAFLD. There were 323 individuals (191 without AMI and 132 with AMI) in T2DM co-existent NAFLD patients who had serum samples, and serum FSTL3 was tested and mediation effect of FSTL3 in association of NAFLD fibrosis and AMI was performed. Results First, increased NAFLD fibrosis risk was an independent risk factor for AMI in patients with T2DM and co-existent NAFLD. In addition, analysis of Gene Expression Omnibus (GEO) database and immunohistochemical staining confirmed the increased expression of FSTL3 in the liver of NAFLD patients with fibrosis. Serum FSTL3 significantly increased in patients with high NAFLD fibrosis risk and AMI, and closely associated with NAFLD fibrosis and AMI severity in T2DM patients with co-existent NAFLD. Most importantly, analysis of the level of mediation revealed that increased serum FSTL3 partially mediated the association of increased NAFLD fibrosis risk with AMI in T2DM patients with co-existent NAFLD. Conclusions NAFLD fibrosis was closely associated with AMI in T2DM patients. FSTL3 expression was enriched in the liver of NAFLD patients with significant and advanced fibrosis, and serum FSTL3 partially mediated the association of increased liver fibrosis risk with AMI in T2DM patients.
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spelling doaj.art-8328d92b98a94386a1c2081d63b5db342023-11-05T12:06:59ZengBMCCardiovascular Diabetology1475-28402023-10-0122111310.1186/s12933-023-02024-xFSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitusWenfei Duan0Ruixiao Shi1Fang Yang2Zhoujunhao Zhou3Lihong Wang4Zhe Huang5Shufei Zang6Department of Endocrinology, The Fifth People’s Hospital of Shanghai, Fudan UniversityDepartment of Traditional Chinese Medicine, Maqiao Community Health Service CenterDepartment of Genetics and Developmental Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityDepartment of Endocrinology, The Fifth People’s Hospital of Shanghai, Fudan UniversityDepartment of Endocrinology, The Fifth People’s Hospital of Shanghai, Fudan UniversityDepartment of Genetics and Developmental Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong UniversityDepartment of Endocrinology, The Fifth People’s Hospital of Shanghai, Fudan UniversityAbstract Background The study aimed to investigate an association of increased liver fibrosis with acute myocardial infarction (AMI), and to investigate the mediating effect of serum follistatin-like protein 3 (FSTL3) on the association in patients with type 2 diabetes mellitus (T2DM). Method A total of 1424 participants were included in this study, and were firstly divided into two groups: 429 T2DM patients and 995 T2DM patients with NAFLD to assess the association of NAFLD and AMI. Then 995 T2DM co-existent NAFLD patients were categorized by NAFLD fibrosis risk to explore the association between NAFLD fibrosis risk and AMI. Immunohistochemistry staining and semi-quantitative analysis of liver FSTL3 were performed in 60 patients with NAFLD. There were 323 individuals (191 without AMI and 132 with AMI) in T2DM co-existent NAFLD patients who had serum samples, and serum FSTL3 was tested and mediation effect of FSTL3 in association of NAFLD fibrosis and AMI was performed. Results First, increased NAFLD fibrosis risk was an independent risk factor for AMI in patients with T2DM and co-existent NAFLD. In addition, analysis of Gene Expression Omnibus (GEO) database and immunohistochemical staining confirmed the increased expression of FSTL3 in the liver of NAFLD patients with fibrosis. Serum FSTL3 significantly increased in patients with high NAFLD fibrosis risk and AMI, and closely associated with NAFLD fibrosis and AMI severity in T2DM patients with co-existent NAFLD. Most importantly, analysis of the level of mediation revealed that increased serum FSTL3 partially mediated the association of increased NAFLD fibrosis risk with AMI in T2DM patients with co-existent NAFLD. Conclusions NAFLD fibrosis was closely associated with AMI in T2DM patients. FSTL3 expression was enriched in the liver of NAFLD patients with significant and advanced fibrosis, and serum FSTL3 partially mediated the association of increased liver fibrosis risk with AMI in T2DM patients.https://doi.org/10.1186/s12933-023-02024-xNonalcoholic fatty liver diseaseLiver fibrosisType 2 diabetes mellitusAcute myocardial infarctionNoninvasive biomarkers
spellingShingle Wenfei Duan
Ruixiao Shi
Fang Yang
Zhoujunhao Zhou
Lihong Wang
Zhe Huang
Shufei Zang
FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus
Cardiovascular Diabetology
Nonalcoholic fatty liver disease
Liver fibrosis
Type 2 diabetes mellitus
Acute myocardial infarction
Noninvasive biomarkers
title FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus
title_full FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus
title_fullStr FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus
title_full_unstemmed FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus
title_short FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus
title_sort fstl3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus
topic Nonalcoholic fatty liver disease
Liver fibrosis
Type 2 diabetes mellitus
Acute myocardial infarction
Noninvasive biomarkers
url https://doi.org/10.1186/s12933-023-02024-x
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