Interferon signaling in myocardial infarction: mechanistic insights and translational prospects

Inflammation following myocardial infarction (MI) is a key determinant of patient prognosis; however, existing anti-inflammatory strategies remain limited in terms of overall benefit, patient eligibility, and safety, creating an urgent need for the development of new anti-inflammatory approaches. Interferon (IFN) signaling permeates the entire process of inflammation and repair following MI. During the inflammatory phase, the cGAS-STING-mediated IFN-I response promotes inflammatory damage; during the proliferative phase, sustained IFN signaling delays the resolution of inflammation and impedes scar formation, whereas moderate IFN signaling promotes resolution; during the maturation phase, IFN signaling can both limit excessive fibrosis and promote low-grade inflammation, scar instability, and the progression of ischemic heart failure. Therefore, precisely identifying the spatiotemporal windows with clear pathogenic roles is of great significance for the translation of IFN signaling. Compared to the bidirectional effects of IFN signaling during the proliferation and maturation phases, the cGAS-STING axis, with its clearly pro-inflammatory role during the inflammatory phase, holds greater translational potential. The development of tissue-specific cGAS-STING inhibitors based on nanodelivery, restricted to short-term application during the acute inflammatory phase of MI, may offer a new therapeutic direction for post-MI anti-inflammatory strategies. Furthermore, in-depth analysis of IFN signaling in conjunction with clinical cohorts in future studies will further aid in the development of precise immunomodulatory strategies for MI.