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Peer-reviewedCC BY 4.0Frontiers in Cardiovascular Medicine

Finerenone attenuates experimental autoimmune myocarditis and modulates cardiac macrophage and Th17-cell responses

  • Pengchong Du1,2,3,4
  • Yameng Zhao1,2,3,4
  • Rilige Su1,2,3,4
  • Ke Hu1,2,3,4
  • Lingyu Bai1,2,3,4
  • Xinyue Cui1,2,3,4
  • Zhaowei Sun1,2,3,4
  • Yu Yang1,2,3,4
  • Xieze Wei5
  • Bolin Jiao1,2,3,4
  • Siyu Guan1,2,3,4
  • Deheng Han1,2,3,4
3 more authors
  • Yang Lu1,2,3,4
  • Jinying Zhang1,2,3,4
  • Junnan Tang1,2,3,4
5 affiliations
  1. 1Department of Cardiology, First Affiliated Hospital of Zhengzhou University
  2. 2Key Laboratory of Cardiac Injury and Repair of Henan Province
  3. 3Henan Province Clinical Research Center for Cardiovascular Diseases
  4. 4State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences
  5. 5Faculty of Medicine, Rheinische Friedrich-Wilhelms-Universitat Bonn
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Abstract

Introduction: Autoimmune myocarditis is characterized by immune-mediated myocardial injury and remodeling. However, whether the selective nonsteroidal mineralocorticoid receptor antagonist finerenone modulates the cardiac cellular microenvironment in autoimmune myocarditis remains unclear. This study aimed to investigate the effects of finerenone on experimental autoimmune myocarditis (EAM) and its regulation of the cardiac cellular microenvironment.

Methods: An EAM model was established in BALB/c mice by α -myosin heavy chain immunization, followed by finerenone treatment. Echocardiography, histopathology, immunohistochemistry, and RT-qPCR were used to evaluate cardiac injury, inflammation, fibrosis, and function. Single-cell RNA sequencing, T-cell receptor clonotype analysis, transcription factor regulatory network analysis, and cell-cell communication analysis were performed to characterize finerenone-induced changes in cardiac immune and stromal cell populations. Flow cytometry and macrophage-CD4 ₊ T-cell co-culture experiments were performed to further validate the immune-related findings.

Results: Finerenone alleviated myocardial injury, inflammatory infiltration, and collagen deposition and improved left ventricular systolic function in EAM mice, including under a delayed-treatment regimen. Single-cell transcriptomic analysis revealed that finerenone remodeled the cardiac cellular microenvironment, reduced remodeling-associated Spp1 ₊ macrophages and inflammation-associated Cxcl10 ₊ macrophages, and suppressed IRF7-, STAT1-, STAT2-, and RFX5-associated transcriptional programs. Finerenone also reduced Th17-related inflammatory and cytotoxic programs and T-cell clonal expansion. Cell-cell communication analysis predicted reduced macrophage-Th17-cell communication, particularly MHC-II-associated signaling. Furthermore, macrophage-CD4 ₊ T-cell co-cultures from finerenone-treated EAM mice exhibited reduced CD4 ₊ T-cell proliferation and IL-17A ₊ CD4 ₊ T-cell proportions compared with those from untreated EAM mice. Profibrotic fibroblast programs and neutrophil inflammatory signaling were also suppressed.

Discussion: Targeting mineralocorticoid receptor-related immune networks may represent a potential therapeutic strategy for autoimmune myocarditis.

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Cite

BibTeXRIS
BibTeX
@article{du2026finerenone,
  title = {{Finerenone attenuates experimental autoimmune myocarditis and modulates cardiac macrophage and Th17-cell responses}},
  author = {Pengchong Du and Yameng Zhao and Rilige Su and Ke Hu and Lingyu Bai and Xinyue Cui and Zhaowei Sun and Yu Yang and Xieze Wei and Bolin Jiao and Siyu Guan and Deheng Han and Yang Lu and Jinying Zhang and Junnan Tang},
  journal = {Frontiers in Cardiovascular Medicine},
  year = {2026},
  month = nov,
  doi = {10.3389/fcvm.2026.2018213},
  url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.2018213/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Finerenone attenuates experimental autoimmune myocarditis and modulates cardiac macrophage and Th17-cell responses
AU  - Pengchong Du
AU  - Yameng Zhao
AU  - Rilige Su
AU  - Ke Hu
AU  - Lingyu Bai
AU  - Xinyue Cui
AU  - Zhaowei Sun
AU  - Yu Yang
AU  - Xieze Wei
AU  - Bolin Jiao
AU  - Siyu Guan
AU  - Deheng Han
AU  - Yang Lu
AU  - Jinying Zhang
AU  - Junnan Tang
PY  - 2026
DA  - 2026/11/05
JO  - Frontiers in Cardiovascular Medicine
DO  - 10.3389/fcvm.2026.2018213
UR  - https://www.frontiersin.org/articles/10.3389/fcvm.2026.2018213/full
AB  - Introduction: Autoimmune myocarditis is characterized by immune-mediated myocardial injury and remodeling. However, whether the selective nonsteroidal mineralocorticoid receptor antagonist finerenone modulates the cardiac cellular microenvironment in autoimmune myocarditis remains unclear. This study aimed to investigate the effects of finerenone on experimental autoimmune myocarditis (EAM) and its regulation of the cardiac cellular microenvironment.  Methods: An EAM model was established in BALB/c mice by α -myosin heavy chain immunization, followed by finerenone treatment. Echocardiography, histopathology, immunohistochemistry, and RT-qPCR were used to evaluate cardiac injury, inflammation, fibrosis, and function. Single-cell RNA sequencing, T-cell receptor clonotype analysis, transcription factor regulatory network analysis, and cell-cell communication analysis were performed to characterize finerenone-induced changes in cardiac immune and stromal cell populations. Flow cytometry and macrophage-CD4 ₊ T-cell co-culture experiments were performed to further validate the immune-related findings.  Results: Finerenone alleviated myocardial injury, inflammatory infiltration, and collagen deposition and improved left ventricular systolic function in EAM mice, including under a delayed-treatment regimen. Single-cell transcriptomic analysis revealed that finerenone remodeled the cardiac cellular microenvironment, reduced remodeling-associated Spp1 ₊ macrophages and inflammation-associated Cxcl10 ₊ macrophages, and suppressed IRF7-, STAT1-, STAT2-, and RFX5-associated transcriptional programs. Finerenone also reduced Th17-related inflammatory and cytotoxic programs and T-cell clonal expansion. Cell-cell communication analysis predicted reduced macrophage-Th17-cell communication, particularly MHC-II-associated signaling. Furthermore, macrophage-CD4 ₊ T-cell co-cultures from finerenone-treated EAM mice exhibited reduced CD4 ₊ T-cell proliferation and IL-17A ₊ CD4 ₊ T-cell proportions compared with those from untreated EAM mice. Profibrotic fibroblast programs and neutrophil inflammatory signaling were also suppressed.  Discussion: Targeting mineralocorticoid receptor-related immune networks may represent a potential therapeutic strategy for autoimmune myocarditis.
SN  - 2297-055X
ER  -