Neutrophil-secreted CHI3L1 exacerbates cardiac dysfunction and inflammation after myocardial infarction

Myocardial infarction (MI) triggers acute inflammation, marked by neutrophil infiltration. Although neutrophils are central to this response, the exact role of various neutrophil-derived factors is not fully understood. Clinical studies have linked one such enigmatic factor, chitinase-3 like-1, to MI outcomes. Hence, we investigated its role in post-MI remodeling. We found that chitinase-3 like-1 (CHI3L1) is upregulated after MI and secreted by activated neutrophils but does not directly affect neutrophil activity. To assess whether increased CHI3L1 influences ventricular remodeling, we subjected mice to non-reperfused MI and administered recombinant CHI3L1. Increased CHI3L1 levels worsened ventricular remodeling. In contrast, CHI3L1-deficient mice showed reduced ventricular remodeling after MI. To explore the underlying mechanisms, we assessed interactions with other cells known to be important in ventricular remodeling. Immunoprofiling of infarcted CHI3L1-deficient mouse hearts revealed a faster decline in neutrophil and monocyte numbers, indicating quicker resolution of inflammation. These findings provide direct evidence that CHI3L1 exacerbates ventricular inflammation and remodeling following MI through gain- and loss-of-function approaches.