Endothelial progenitor cells in chronic obstructive pulmonary disease

Introduction Chronic obstructive pulmonary disease is a degenerative, life-threatening lung disease defined by a persistent poor airflow. Pulmonary vascular endothelial dysfunction is a characteristic pathological finding of chronic obstructive pulmonary disease. Endothelial progenitor cells are a population of adult stem cells mobilised from the bone marrow into the circulation, with the function of maintaining vascular homeostasis. Decreasing number of endothelial progenitor cells has been established as a prognostic risk factor associated with endothelial dysfunction and high cardiovascular risk. In chronic obstructive pulmonary disease, few studies to date have investigated the number of endothelial progenitor cells with conflicting results. Quantification of endothelial progenitor cells is affected by high individual variability. Age, gender, smoking habit, cardiovascular comorbidities, different cell populations examined, different methodologies used or the sample size of the study, all are variables that can influence endothelial progenitor cell numbers. This review tries to comprehend why these discrepancies in endothelial progenitor cell numbers occur and sets strategies to encourage greater confidence in the reproducibility of the results, a basis for future stem cell therapy studies. Conclusion Greater confidence in the reproducibility of the quantification of EPCs taking into account all possible variables is necessary before using them as the basis for detailed mechanistic investigations and stem cell therapy. Introduction Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a degenerative, lifethreatening lung disease, affecting an estimated 329 million people and accounting for 5% of all deaths globally per year1. Mortality is expected to increase due to a rise in smoking rates and an aging population in many countries. The World Health Organization predicts that COPD will become the third leading cause of death worldwide by 20301. Unfortunately, COPD is not curable and cannot be reversed. Drug treatment can improve symptoms and minimise further damage, but does not alter the underlying progression of this disease. Thus, COPD is a major public health problem with high prevalence, increasing incidence and elevated associated socioeconomic costs. Post-bronchodilator spirometry is required for the diagnosis and assessment of severity of COPD2. Is defined by a persistent poor airflow (FEV1/FVC < 0.70), which results from an inflammatory process affecting the airways and lung parenchyma usually in the form of emphysema2. Chronic and acute inflammation induced by the inhalation of noxious particles, mainly cigarette smoking (CS), is the primary pathogenesis of COPD3. Genetic factors and aging effects are also involved in the disease progression. Vascular change and angiogenesis is an integral part of the pulmonary inflammatory response. The lung is exposed to external challenges such as inhaled particles, toxic gases or infections every day; the defence against these external injuries depends on the immune system and the efficiency of the system to remove and replace apoptotic injured cells4. CS not only causes inflammation and direct injury to lung tissue but also inhibits compensatory angiogenesis and thus impairs repair and adaptive mechanisms in the lung. The aim of this review was to discuss endothelial progenitor cells (EPCs) in COPD. Discussion COPD and endothelial dysfunction Pulmonary vascular endothelial dysfunction is a characteristic pathological finding of COPD. Studies have shown alterations in the vessel structure and an abnormal functional associated with an atypical control of endothelial cellular growth and resistance to apoptosis in the endothelium of patients suffering from COPD5,6. Growing evidence suggests that the endothelial cell damage and dysfunction found in pulmonary vessels of these patients is an initial and important triggering factor that promotes pulmonary vasculature remodelling and, hence, pulmonary hypertension in COPD7. It is been recognised that patients with COPD showed an endothelial impairment in both pulmonary and systemic circulation at early stages of the disease4,8. In addition, scanning electron microscopy of the endothelial surface * Corresponding author Email: tura@clinic.ub.es Department of Pulmonary Medicine, Hospital Clinic-Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias, Spain 08036 Barcelona, Spain.