The Role of the PD-1/PD-L1 Immune Checkpoint Pathway in Myocardial Infarction: A Review from Pathophysiological Mechanisms to Therapeutic Strategies

Zilong Luo¹Chloe Zhang^1,2Junjie Zong^1,2Jun Hu¹Pinyan Huang^1,2Yuqing Niu¹Cheng Zhou^2,3*Song Wang^1,2*Dan Zhang^4*

• ¹Department of Cardiovascular Surgery, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, China
• ²Center for Translational Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
• ³Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
• ⁴Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), are vital molecules in immune checkpoints, significantly impacting cancer treatment. Recent studies have increasingly highlighted the complex roles of the PD-1/PD-L1 pathway in cardiovascular diseases, particularly in myocardial infarction (MI). In addition to being involved in immune modulation and the inflammatory response post-myocardial ischemia, this pathway is also crucial for myocardial repair and regeneration. Additionally, the clinical application of PD-1/PD-L1 immune checkpoint inhibitors has led to groundbreaking advances in cancer treatment; however, concerns regarding cardiotoxicity and myocardial injury as adverse events have also been raised. This review systematically examines the pathophysiological mechanisms of the PD-1/PD-L1 pathway in myocardial infarction, explores its potential as a therapeutic target, and assesses the adverse cardiovascular reactions associated with existing immune checkpoint inhibitors and management strategies. The aim of this study was to provide a theoretical basis and clinical guidance for future immunotherapeutic approaches for treating myocardial infarction.