The role of bone marrow-derived endothelial progenitor cells and angiogenic responses in chronic obstructive pulmonary disease

Abstract

Increased vascularity of the bronchial sub-mucosa is a cardinal feature of chronic obstructive pulmonary disease (COPD) and is associated with disease severity. Capillary engorgement, leakage, and vasodilatation can directly increase airway wall thickness resulting in airway luminal narrowing and facilitate inflammatory cell trafficking, thereby contributing to irreversible airflow obstruction, a characteristic of COPD. Airway wall neovascularisation, seen as increases in both the size and number of bronchial blood vessels is a prominent feature of COPD that correlates with reticular basement membrane thickening and airway obstruction. Sub-epithelial vascularization may be an important remodelling event for airway narrowing and airflow obstruction in COPD. Post-natal angiogenesis is a complex process, whereby new blood vessels sprouting from extant microvasculature, can arise from the proliferation of resident mature vascular endothelial cells (ECs). In addition, this may arise from increased turnover and lung-homing of circulating endothelial progenitor cells (EPCs) from the bone marrow (BM). Following lung-homing, EPCs can differentiate locally within the tissue into ECs, further contributing to vascular repair, maintenance, and expansion under pathological conditions, governed by a locally elaborated milieu of growth factors (GFs). In this article, we will review evidence for the role of BM-derived EPCs in the development of angiogenesis in the lug and discuss how this may relate to the pathogenesis of COPD.

Endothelial Progenitor Cells as Pathogenetic and Diagnostic Factors, and Potential Targets for GLP-1 in Combination with Metabolic Syndrome and Chronic Obstructive Pulmonary Disease

“…However, the EPS population is not homogeneous. EPC is defined as CD34 + VEGFR2 + CD45 dim [ 36 ]. Other authors use coexpression of CD34 and fibroblast growth factor receptor 1 to identify EPC [ 37 ].…”

PU.1 alleviates the inhibitory effects of cigarette smoke on endothelial progenitor cell function and lung-homing through Wnt/β-catenin and CXCL12/CXCR4 pathways

“…Our previous work also showed that EPCs treated with CSE in vitro displayed decreased capacities of proliferation, adhesion, and secretion 29 . Moreover, extensive data have established that circulating EPCs are decreased in COPD subjects 30 , but the enumeration of EPCs homing into the lungs of COPD patients has not been studied. In this study, we explored the EPCs homing into the lung and investigated the protective effect of PU.1 for the first time in CSE-induced emphysematous mice.…”

Hyperhomocysteinemia induced endothelial progenitor cells dysfunction through hyper-methylation of CBS promoter

“…The presence of BM-EPC in bone milieu contributes to bone marrow angiogenesis [2,14]. In regenerative medicine, BM-derived EPCs could potentially be used as therapeutic strategies to combat several diseases, including wound healing, myocardial infarction, and chronic obstructive pulmonary disease [15–18]. Both hypercholesteremia and HHcy are accepted as common risk factors for the development of vascular disease, thus limiting EPC-mediated vascular repair [19,20].…”