Anti-atherogenic immune checkpoint TIM-3 as a promising pharmacologic target toward ischemic heart diseases: a prospective review.

Recently, immunogene therapy has been of great interest in cardiovascular diseases. In this regard, various immune checkpoint inhibitors (ICIs) are identified to have a crucial role in regulating inflammatory responses. The T-cell immunoglobulin and mucin-domain containing molecule-3 (TIM-3, CD366), a relatively newly discovered group of molecules with a conserved structure, has emerged as a critical immune checkpoint with significant regulatory roles in cardiovascular inflammation and atherosclerosis. This prospective review explores the importance of TIM-3 in modulating immune responses relevant to ischemic heart diseases (IHD), highlighting its interactions with inflammatory pathways such as Toll-like receptor-4 (TLR-4). TIM-3, predominantly expressed on T cells, dendritic cells, and monocytes, acts as an inhibitory receptor that quenches pro-inflammatory signaling, particularly upon binding to ligands like galectin-9. Noteworthy, recent evidence suggests that TIM-3 deficiency or dysregulation can exacerbate inflammatory cascades, contributing to the progression of IHD and related complications. Here, the therapeutic potential of targeting TIM-3 for the management of IHD, especially in the settings of systemic inflammation and post-operative complications, has been discussed. By elucidating the molecular mechanisms and translational prospects of TIM-3 modulation, this work proposes new avenues for immunotherapeutic intervention in cardiovascular disease and post-operative SIRS, warranting further research in clinical trials.