The extracellular CIRP as a predictive marker for the endothelial dysfunction in chronic obstructive pulmonary disease combined with pulmonary hypertension

Abstract

Background: Pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD), distinguished by pulmonary endothelial dysfunction. The extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern (DAMP) that triggers inflammation and causes vascular endothelial dysfunction in COPD-PH. Methods: The expression levels of CIRP were compared in peripheral lung tissues among 40 individuals. Moreover, A prospective analysis was conducted on serum levels of eCIRP, interleukin (IL) 1β, IL-33, endothelin-1 (ET-1), and nitric oxide (NO) in 150 COPD patients and 50 healthy control individuals at Jiangsu Taizhou Peoples Hospital. The study aimed to compare these serum levels and correlations among COPD-PH group, COPD non-PH group and the normal group. Results: We found higher CIRP levels in COPD-PH compared to COPD non-PH and the normal in lung tissue samples. A prospective analysis showed higher serum levels of eCIRP, IL-1β, IL-33, and ET 1 in COPD-PH, while a noticeable reduction in NO levels. There exists a correlation between the severity of COPD-PH and elevated levels of eCIRP, proinflammatory cytokines like IL-1β and IL-33, along with indicators of endothelial dysfunction like endothelin-1 ET-1 and NO. Moreover, the serum eCIRP level demonstrated a notable positive correlation with the levels of IL-1β, IL-33, PCT, and ET-1, while displaying a negative correlation with NO and Peripheral Oxygen Saturation (SpO2). Moreover, the serum eCIRP level demonstrated a notable positive correlation with the levels of IL-1β, IL-33, PCT, and ET-1, while displaying a negative correlation with NO and SpO2. Moreover, an assessment of independent risk factors for COPD-PH with ROC curve analysis, gauged the predictive value of serum eCIRP, IL-1β, IL-33, ET-1, and NO levels in diagnosing COPD-PH. Elevated eCIRP, IL-33, and ET-1 levels significantly correlated with COPD-PH, highlighting eCIRP’s strong predictive value for this condition. Conclusion: eCIRP levels could serve as a valuable biomarker for predicting endothelial dysfunction in COPD-PH.