Role of the RAGE signaling pathway in myocardial ischemia/reperfusion injury.

The receptor for advanced glycation end products (RAGE), a multi-ligand receptor of the immunoglobulin superfamily, plays a pivotal regulatory role in myocardial ischemia/reperfusion (I/R) injury. This review summarizes the regulatory mechanisms governing RAGE expression; the dynamic alterations of its major ligands-advanced glycation end products (AGEs), high mobility group box 1 (HMGB1), and the S100 protein family-during myocardial I/R; and the multifaceted pathological mechanisms by which RAGE-mediated downstream signaling pathways, including activation of the MAPK and JAK/STAT cascades and suppression of the pro-survival PI3K/AKT pathway, exacerbate myocardial injury in the setting of I/R. Furthermore, this review synthesizes RAGE-targeted therapeutic strategies, such as small-molecule inhibitors and soluble RAGE (sRAGE), and discusses their prospects for clinical translation, thereby providing a theoretical framework for myocardial protection strategies centered on the RAGE signaling pathway.