The role and mechanism study of Cxcl14 in chronic critically ill cardiac dysfunction.

Objective: To investigate the role and mechanism of Cxcl14 in cardiac function impairment in chronic critical illness (CCI).

Method: Clinical data from CCI patients with heart failure and uncomplicated CCI cases were collected. Serum Cxcl14 concentrations were quantified via ELISA. A CCI heart function injury mouse model (CLP model) was established, and the heart function and morphological indicators was measured. The inflammatory infiltration of myocardial tissue, the Cxcl4 expression levels and myocardial fibrosis related proteins, and the alleviating effect of anti-Cxcl14 antibody on CCI cardiac dysfunction was detected.

Result: The serum level of Cxcl14 was found to exhibit a positive correlation with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and a negative correlation with left ventricular ejection fraction (LVEF) in patients with CCI. Subsequent investigations into the role of Cxcl14 in CCI-related cardiac dysfunction revealed significant findings. In the CLP model, Cxcl14 was shown to reduce both LVEF and left ventricular intramural shortening fraction (LVFS), while simultaneously increasing the expression of α-smooth muscle actin (α-SMA) and collagen III in myocardial tissue. Additionally, Cxcl14 elevated the levels of ED-1, myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), promoting inflammatory cell infiltration in the myocardium. Administration of an anti-Cxcl14 antibody mitigated these effects, providing a potential therapeutic intervention.

Conclusion: The expression of Cxcl14 was positively associated with the onset and severity of cardiac dysfunction in CCI patients. In the CLP mouse model, Cxcl14 aggravated myocardial injury and fibrosis, while promoting the infiltration of inflammatory cells into myocardial tissue.