The possible mechanisms linking chronic obstructive pulmonary disease and coronary atherosclerosis based on coronary computed tomography angiography and animal experiments

Objective The study sought to evaluate the characteristics of coronary atherosclerosis (CAS) in patients with chronic obstructive pulmonary disease (COPD) based on computed tomography angiography (CTA), explore its relationship with COPD, and discuss the mechanisms of KEAP1–NRF2-mediated oxidative stress. Methods A total of 300 COPD patients undergoing CTA were divided into COPD alone (n = 165) and COPD + CAS (n = 135) groups based on the presence/absence of CAS, and 120 CAS patients were enrolled as controls. Clinical and laboratory data were collected and compared. Patients were further stratified regarding COPD severity (76 mild, 84 moderate, 74 severe, and 68 very severe cases). Univariate/multivariate logistic regression identified factors influencing COPD with CAS. In vivo validation of KEAP1–NRF2-mediated oxidative stress was performed for mechanistic interpretation using a COPD and CAS comorbidity model. Results Compared with patients with CAS or COPD alone, significant differences in terms of clinical baseline data were observed in patients with COPD and CAS. COPD patients exhibited reduced KEAP1, superoxide dismutase, and catalase activities, along with upregulated NRF2, reactive oxygen species, and malondialdehyde. These alterations were more pronounced in patients with more severe COPD and concomitant CAS. KEAP1 and NRF2 were independent influencing factors of comorbid COPD and CAS. In the mouse model, activating the KEAP1–NRF2-mediated oxidative stress was associated with aggravated lung injury and enlarged atherosclerotic lesion areas. Conclusion COPD severity is closely associated with the burden of CAS. Dysregulation of the KEAP1–NRF2-mediated oxidative stress may represent a shared biological feature linking COPD and CAS.