Simulating Cor pulmonale in chronic obstructive pulmonary disease via cigarette smoke exposure and left pulmonary artery ligation in mice

Cor pulmonale, indicative of right heart failure (RHF), is precipitated by pulmonary conditions that escalate pulmonary arterial pressure. This complication is notably prevalent in patients with chronic obstructive pulmonary disease (COPD), and is recognized as an independent predictor of adverse outcomes. Despite its significance, the lack of appropriate animal models has hindered the development of therapies for cor pulmonale in COPD patients. Therefore, we aimed to establish a mouse model that mimics the essential pathological features of COPD-cor pulmonale. All mice underwent thoracic surgery, including left pulmonary artery ligation (LPAL) or sham surgery (artery exposed without ligation). Following a 2-week recuperation, the mice were exposed to cigarette smoke or room air for 28 weeks. At the end of the exposure, pulmonary function, right ventricular hemodynamics, and histological alterations were determined. CD31, α-SMA, and CD68 were detected by immunofluorescence and immunohistochemistry to show vascular and macrophage changes. Mice subjected to LPAL and cigarette smoke exposure exhibited COPD-like features, including impaired lung function, emphysematous alterations, pulmonary inflammatory cell infiltration, and airway remodeling, accompanied by the increase in right ventricular systolic pressure, right ventricular hypertrophy, fibrosis, macrophage aggregation, and reduced capillary density. This model, integrating cigarette smoke exposure with LPAL, effectively replicates the critical pathological features of COPD-cor pulmonale.