S100a9 lactylation triggers neutrophil trafficking and cardiac inflammation in myocardial ischemia/reperfusion injury.

ABSTRACT: Lactylation, a posttranslational modification derived from glycolysis, plays a pivotal role in ischemic heart disease. Neutrophils are predominantly glycolytic cells that trigger intensive inflammation of myocardial ischemia/reperfusion (MI/R). However, whether lactylation regulates neutrophil function during MI/R remains unknown. We applied lactyl proteomics analysis and found that S100a9 was lactylated at lysine 26 (S100a9K26la) in neutrophils, with elevated levels observed in both patients with acute myocardial infarction (AMI) and MI/R model mice. We demonstrated that S100a9K26la drove the development of MI/R using mutant knockin mice. Mechanistically, lactylated S100a9 translocated to the nucleus of neutrophils, where it bound to the promoters of migration-related genes, thereby enhan

SUBMITTER: Wang X 

PROVIDER: S-EPMC12700540 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature