Progenitor cell mobilisation and recruitment in pulmonary arteries in chronic obstructive pulmonary disease

Abstract

Background Pulmonary vascular abnormalities are a characteristic feature of chronic obstructive pulmonary disease (COPD). Cigarette smoking is the most important risk factor for COPD. It is believed that its constant exposure triggers endothelial cell damage and vascular remodelling. Under pathological conditions, progenitor cells (PCs) are mobilized from the bone marrow and recruited to sites of vascular injury. The aim of the study was to investigate whether in COPD the number of circulating PCs is related to the presence of bone marrow-derived cells in pulmonary arteries and the association of these phenomena to both systemic and pulmonary endothelial dysfunction. Methods Thirty-nine subjects, 25 with COPD, undergoing pulmonary resection because of a localized carcinoma, were included. The number of circulating PCs was assessed by flow cytometry using a triple combination of antibodies against CD45, CD133 and CD34. Infiltrating CD45 + cells were identified by immunohistochemistry in pulmonary arteries. Endothelial function in systemic and pulmonary arteries was measured by flow-mediated dilation and adenosine diphosphate-induced vasodilation, respectively. Results COPD patients had reduced numbers of circulating PCs ( p < 0.05) and increased numbers of CD45 + cells (< 0.05) in the pulmonary arterial wall than non-COPD subjects, being both findings inversely correlated (r = − 0.35, p < 0.05). In pulmonary arteries, the number of CD45 + cells correlated with the severity of vascular remodelling (r = 0.4, p = 0.01) and the endothelium-dependent vasodilation (r = − 0.3, p = 0.05). Systemic endothelial function was unrelated to the number of circulating PCs and changes in pulmonary vessels. Conclusion In COPD, the decrease of circulating PCs is associated with their recruitment in pulmonary arteries, which in turn is associated with endothelial dysfunction and vessel remodelling, suggesting a mechanistic link between these phenomena. Our findings are consistent with the notion of an imbalance between endothelial damage and repair capacity in the pathogenesis of pulmonary vascular abnormalities in COPD. Electronic supplementary material The online version of this article (10.1186/s12931-019-1024-z) contains supplementary material, which is available to authorized users.

The vascular perspective on acute and chronic lung disease

“…In the pulmonary arterial wall of patients with COPD, an increase in the number of CD45 + cells has been observed, along with a decrease in the number of circulating progenitor cells. These changes were associated with endothelial dysfunction and vessel remodeling ( 146 ). In the adventitial layer, total leukocytes increase, especially CD8 + T cells, albeit with no changes in neutrophil or macrophage numbers.…”

Forthcoming complications in recovered COVID-19 patients with COPD and asthma; possible therapeutic opportunities

“…The lack of appropriate epithelialization rate and disruption of the mucociliary system cause microbial overload and vulnerability to viral infection. Endothelial layer damage and aberrant vascular remodeling reduce the number of recruited circulating stem cells into the pulmonary niche, resulting in local stem cell exhaustion, cellular senescence, and reduced regeneration capacity [81][82][83].…”

Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target

“…Intratracheal application of bone marrow-derived EPCs attenuated the development of pulmonary emphysema in mice exposed to CS in a long term murine study, via the alleviation of inflammatory infiltration, decreased proteolytic enzyme activity, and improved antioxidant activity (298). In contrast, enhanced progenitor cell numbers in pulmonary arteries obtained from patients with COPD were associated with decreased endothelium-dependent dilation and inversely correlated with arterial lumen area (299). However, the characterization of these cells by progenitor marker expression was limited in this study.…”

“…However, the characterization of these cells by progenitor marker expression was limited in this study. As the level of circulating EPCs is decreased but their migratory potential and adhesion is increased in COPD, it was suggested that circulating ECs are recruited to pulmonary tissue in COPD (296,299,300). This might not be beneficial in COPD patients, since circulating progenitor cells in these patients show impaired angiogenic ability, increased apoptosis, and impaired NO production compared with these features of EPCs obtained from healthy, non-smoking controls (301,302).…”