The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications

  • Signal Transduct Target Ther. 2025 May 23;10(1):166. doi: 10.1038/s41392-025-02220-z.
Xiaoyan Wang  #  1  2 ,  Liming Chen  #  3  4 ,  Jianming Wei  #  5 ,  Hao Zheng  #  6 ,  Ning Zhou  #  7 ,  Xinjie Xu  8 ,  Xin Deng  3  4 ,  Tao Liu  9  10  11 ,  Yunzeng Zou  12  13  14
Affiliations
  • 1. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China. [email protected].
  • 2. State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China. [email protected].
  • 3. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • 4. State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 5. Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.
  • 6. Jiangsu Provincial Key Laboratory of Critical Care Medicine and Department of Critical Care Medicine, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China.
  • 7. Department of Cardiovascular Medicine, Anzhen Hospital Affiliated to Capital Medical University, Beijing, China.
  • 8. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 9. Jiangsu Provincial Key Laboratory of Critical Care Medicine and Department of Critical Care Medicine, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China. [email protected].
  • 10. Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Jiangsu, Nanjing, China. [email protected].
  • 11. State Key Laboratory of Respiratory Disease, Joint International Research Laboratory of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. [email protected].
  • 12. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China. [email protected].
  • 13. State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China. [email protected].
  • 14. Institutes of Advanced Medical Sciences and Huaihe Hospital, Henan University, Kaifeng, Henan, China. [email protected].
  • # Contributed equally.
PMID: 40404619 DOI: 10.1038/s41392-025-02220-z
Abstract

Immune system plays a crucial role in the physiological and pathological regulation of the cardiovascular system. The exploration history and milestones of immune system in cardiovascular diseases (CVDs) have evolved from the initial discovery of chronic inflammation in atherosclerosis to large-scale clinical studies confirming the importance of anti-inflammatory therapy in treating CVDs. This progress has been facilitated by advancements in various technological approaches, including multi-omics analysis (single-cell Sequencing, spatial transcriptome et al.) and significant improvements in immunotherapy techniques such as chimeric antigen receptor (CAR)-T cell therapy. Both innate and adaptive immunity holds a pivotal role in CVDs, involving Toll-like Receptor (TLR) signaling pathway, nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2) signaling pathway, inflammasome signaling pathway, RNA and DNA sensing signaling pathway, as well as antibody-mediated and complement-dependent systems. Meanwhile, immune responses are simultaneously regulated by multi-level regulations in CVDs, including Epigenetics (DNA, RNA, protein) and Other key signaling pathways in CVDs, interactions among immune cells, and interactions between immune and cardiac or vascular cells. Remarkably, based on the progress in basic research on immune responses in the cardiovascular system, significant advancements have also been made in pre-clinical and clinical studies of immunotherapy. This review provides an overview of the role of immune system in the cardiovascular system, providing in-depth insights into the physiological and pathological regulation of immune responses in various CVDs, highlighting the impact of multi-level regulation of immune responses in CVDs. Finally, we also discuss pre-clinical and clinical strategies targeting the immune system and translational implications in CVDs.