Patient studies show that chitinase 3-like 1 (CHI3L1) is a novel biomarker of coronary artery disease (CAD). Furthermore, CHI3L1 plasma level is a strong predictor of all-cause of mortality in patients with CAD, and is a strong indicator of heart failure progression. Studies from our lab revealed that CHI3L1 is elevated in hearts after MI, and systemic administration of CHI3L1 in mice exacerbated post-MI fibrosis and left ventricular dysfunction. The goal of the current study was to delineate the mechanism of CHI3L1 secretion after MI and test the impact of CHI3L1 on post-MI replacement fibrosis. We found that CHI3L1 levels were rapidly increased in infarcted regions of LV at 2 d after MI and remained significantly elevated at 7 and 35 d (n=5-11/group, p Chil1 -/- subjected to permanent coronary artery ligation showed decreased end-systolic and diastolic volumes and increased ejection fraction measured at 7 and 35 d with echocardiography (n=7-10/group, p Chil1 -/- mice compared to their Chil1 +/+ controls (n=16-18/group, p