LAUSR

Objective: Clinical studies show that chitinase 3-like 1 (CHI3L1) plasma level is a strong predictor of all-cause of mortality in patients with heart failure. Studies from our lab revealed that CHI3L1 is elevated in hearts after MI, and CHI3L1 deficient mice show preservation of ventricular structure and function after MI. Furthermore, we found that neutrophils are the main source of CHI3L1. The studies conducted here seek to identify the mechanism by which CHI3L1 promotes HF progression. Infarct healing is accomplished through the formation of a collagen-based scar, a process that is initiated and orchestrated by the early recruitment of neutrophils. Although early recruitment of neutrophils is necessary for proper infarct healing, prolonged and uncontrolled neutrophilia impairs scar formation and exacerbates ventricular dysfunction after MI. Hypothesis: We hypothesized that CHI3L1 exacerbates cardiac dysfunction via promoting post-MI neutrophilia. Methods: Male and female Chil1-/- and Chil1+/+ mice (n=5 males, 5–6 females,14–24 wk) were subjected to MI via permanent ligation of the LAD coronary artery. At 2 d post-MI, peripheral blood, bone marrow, spleen, and heart were collected and probed with fluorescently labeled antibodies, and flow cytometry was used to quantify neutrophils. Results: No differences in CD11bPosLy6GPos neutrophil recruitment to the heart 2 d post-MI was observed between ChiL1+/+ and Chil1-/- mice in males and females (p = 0.14; p = 0.38). Furthermore, we identified no significant differences in the balance of immature CD11bPosLy6GPosCD101Neg neutrophils recruited post-MI (p = 0.12; p = 0.86). Circulating numbers of CD11bPosLy6GPos and CD11bPosLy6GPosCD101Neg neutrophils in the peripheral blood post-MI were also unchanged between Chil1-/- and Chil1+/+ controls (p = 0.76; p = 0.09). Splenic CD11bPosLy6GPos neutrophils or CD11bPosLy6GPosCD101Neg immature neutrophils were unchanged between Chil1-/- and Chil1+/+ controls (p = 0.69; p = 0.65). The major site of neutrophil production, the bone marrow, also showed no difference in numbers of CD11bPosLy6GPos neutrophils or CD11bPosLy6GPosCD101Neg immature neutrophils between Chil1-/- and Chil1+/+ controls (p = 0.35; p = 0.29). Conclusions: Our data shows that CHI3L1 deficiency does not influence neutrophil production, circulation, or infiltration of the heart at 2 d post-MI. Additionally, we see no differences in surface expression of the neutrophil maturity marker CD101, indicating that CHI3L1 deficiency plays no role in determining the homogeneity of the neutrophil response. The mechanism by which CHI3L1 contributes to HF remains elusive. Future investigations will elucidate how CHI3L1 modulates monocyte and macrophage driven inflammation post-MI. NIH R01 HL141191, NIH P30 GM127607, Jewish Heritage Fund for Excellence, NIH T32 AI132146 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.