ResearchIn-Press PreviewCardiologyCell biology
Open Access | 10.1172/jci.insight.187848
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Yan, Y. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Zhang, T. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by He, X. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by
Du, T.
in:
JCI
|
PubMed
|
Google Scholar
|
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Dai, G. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Xu, X. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by chen, Z. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Wu, J. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Zhou, H. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Peng, Y. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Li, Y. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Liu, C. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Liao, X. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Dong, Y. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Ou, J. in: JCI | PubMed | Google Scholar
1Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Find articles by Huang, Z. in: JCI | PubMed | Google Scholar
Published March 20, 2025 - More info
Inflammation is a critical pathological process in myocardial infarction. Although immunosuppressive therapies can mitigate inflammatory responses and improve outcomes in myocardial infarction, they also increase the risk of infections. Identifying novel regulators of local cardiac inflammation could provide safer therapeutic targets for myocardial ischemia/reperfusion injury. In this study, we identified a previously unknown micropeptide, which we named Inflammation Associated MicroPeptide (IAMP). IAMP is predominantly expressed in cardiac fibroblasts, and its expression is closely associated with cardiac inflammation. Down-regulation of IAMP promotes, whereas its overexpression prevents, the transformation of cardiac fibroblasts into a more inflammatory phenotype under stressed/stimulated conditions, as evidenced by changes in the expression and secretion of pro-inflammatory cytokines. Consequently, loss of IAMP function leads to uncontrolled inflammation and worsens cardiac injury following ischemia/reperfusion surgery. Mechanistically, IAMP promotes the degradation of HIF-1α by interacting with its stabilizing partner HSP90, and thus suppresses the transcription of pro-inflammatory genes downstream of HIF-1α. This study underscores the significance of fibroblast-mediated inflammation in cardiac ischemia/reperfusion injury and highlights the therapeutic potential of targeting micropeptides for myocardial infarction.