Abstract
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.