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

Wenfei Duan; Ruixiao Shi; Fang Yang; Zhoujunhao Zhou; Lihong Wang; Zhe Huang; Shufei Zang

doi:10.1186/s12933-023-02024-x

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

Cardiovasc Diabetol. 2023 Oct 30;22(1):297. doi: 10.1186/s12933-023-02024-x.

Authors

Wenfei Duan^#¹, Ruixiao Shi^#^{2

3}, Fang Yang^#⁴, Zhoujunhao Zhou¹, Lihong Wang¹, Zhe Huang⁵, Shufei Zang⁶

Affiliations

¹ Department of Endocrinology, The Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, China.
² Department of Traditional Chinese Medicine, Maqiao Community Health Service Center, Minhang District, Shanghai, 20111, China.
³ Center of Community-Based Health Research, Fudan University, Shanghai, China.
⁴ Department of Genetics and Developmental Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
⁵ Department of Genetics and Developmental Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China. zhehuang@sjtu.edu.cn.
⁶ Department of Endocrinology, The Fifth People's Hospital of Shanghai, Fudan University, 801 Heqing Road, Minhang District, Shanghai, 200240, China. sophiazsf@fudan.edu.cn.

^# Contributed equally.

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.

Keywords: Acute myocardial infarction; Liver fibrosis; Nonalcoholic fatty liver disease; Noninvasive biomarkers; Type 2 diabetes mellitus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / diagnosis
Diabetes Mellitus, Type 2* / epidemiology
Follistatin-Related Proteins* / genetics
Humans
Liver Cirrhosis / diagnosis
Myocardial Infarction* / complications
Myocardial Infarction* / diagnosis
Myocardial Infarction* / epidemiology
Non-alcoholic Fatty Liver Disease* / complications
Non-alcoholic Fatty Liver Disease* / diagnosis
Non-alcoholic Fatty Liver Disease* / epidemiology

Substances

Follistatin-Related Proteins
Fstl3 protein, human