Characterization of vascular remodelling in experimental emphysema

Rationale: Chronic obstructive pulmonary disease (COPD) is defined as progressive airflow obstruction, featured by emphysema and small airway disease. Pulmonary hypertension is a common complication of COPD and characterized by smooth muscle cell proliferation and vascular remodelling. Here, we sought to elucidate whether pulmonary hypertension developed in elastase-induced experimental emphysema in mice. Methods: Experimental emphysema was induced in C57BL/6 mice by single orotracheal instillation of porcine pancreatic elastase (PPE) (100 U/Kg BW) in 0.08ml of saline solution. Mice were sacrificed at day 14, lungs removed, and fixed with 4% paraformaldehyde. We measured airspace enlargement by quantification of the mean linear chord length (MCL) and surface area. Vascular remodelling was assessed by double immunostaining of alpha-smooth muscle actin (Acta-2) and Ki67 to identify proliferating smooth muscle cells. Results: Expression of Acta-2 was observed in the large blood vessel and airways smooth muscle cells of both healthy and emphysematous mouse lungs. Furthermore, Acta-2 expression was frequently detected in round and spindle-shape fibroblast-like cells in the alveolar septum adjacent to the dilated alveolar structure of emphysematous lungs. Interestingly, co-localisation of Ki67 and Acta-2 was neither detected in smooth muscle cells nor fibroblast like-cells in emphysematous mouse lungs. Conclusions: These results suggest that 1) smooth muscle cells do not exhibit a proliferative phenotype in established experimental emphysema, and 2) activated fibroblast-like cells are a common feature in established experimental emphysema.