Post-translational modifications in sepsis-induced myocardial dysfunction – Molecular mechanisms and therapeutic targets: A review

Sepsis-induced myocardial dysfunction (SIMD) is a frequent and life-threatening complication of sepsis driven by interconnected inflammatory, oxidative, metabolic, and mitochondrial disturbances. Post-translational modifications (PTMs) have emerged as key regulators of these processes by dynamically altering protein activity, stability, localization, and signaling. This narrative review aimed to summarize the roles of major PTMs in SIMD and evaluate their potential as therapeutic targets. Relevant original studies and authoritative reviews published predominantly within the past decade were identified through targeted searches of PubMed and Web of Science and qualitatively synthesized. Current evidence indicates that phosphorylation, acetylation, ubiquitination, protein methylation, ADP-ribosylation, and palmitoylation regulate major pathways involved in myocardial inflammation, oxidative stress, mitochondrial dysfunction, metabolic reprogramming, apoptosis, and impaired contractility. Crosstalk among these modifications further integrates signaling networks, while upstream epigenetic mechanisms, including DNA methylation and N6-methyladenosine RNA modification, can influence PTM-related enzymes and downstream signaling. Experimental studies also suggest that pharmacological modulation of PTM-regulated pathways may attenuate myocardial injury; however, most mechanistic and therapeutic evidence derives from animal models and cultured cells, with limited validation in human septic myocardium. PTMs therefore represent promising mechanistic and therapeutic targets in SIMD, but systematic characterization of PTM crosstalk and rigorous human translational studies are required before PTM-directed strategies can be incorporated into clinical practice.