Fast reduction of peripheral blood endothelial progenitor cells in healthy humans exposed to acute systemic hypoxia

Abstract

Non-technical summary The endothelium is a thin layer of cells lining the interior surface of the entire circulatory system. Endothelial progenitor cells (EPCs) have a crucial role in maintaining the integrity of the endothelium, as they are recruited from the bone marrow to sites of endothelial injury where they contribute to blood vessel formation and repair. The factors regulating EPC mobilization and trafficking remain incompletely understood. We evaluated the time-course effects of a single 4 h bout of severe hypoxic breathing (simulating 4100 m altitude) followed by 4 h restoration in room air. We show that hypoxia alone induces a rapid disappearance of EPCs from blood, probably sustained by a prompt cell marginalization followed by a late increase in EPC apoptosis. These observations may broaden our understanding of the mechanisms operated by EPCs to maintain endothelial homeostasis and may help to elucidate the potential role of EPCs in regenerative medicine.Abstract There are hints that hypoxia exposure may affect the number of circulating endothelial progenitor cells (EPCs) in humans. To test this hypothesis, the concentration of EPCs was determined by flow cytometry in the peripheral blood of 10 young healthy adults before (0 h), at different times (0.5 h, 1 h, 2 h and 4 h) during a 4 h normobaric hypoxic breathing simulating 4100 m altitude, and in the following recovery breathing room air. Results were interpreted mainly on the basis of the changes in surface expression of CXC chemokine receptor-4 (CXCR-4, a chemokine receptor essential for EPC migration and homing) and the percentage of apoptotic cells, the plasmatic levels of markers of oxidative stress induced by hypoxic breathing. Compared to 0 h, the concentration of EPCs, identified as either CD45 dim /CD34 + /KDR + or CD45 dim /CD34 + /KDR + /CD133 + cells, decreased from 337 ± 83 ml −1 (mean ± SEM) to 223 ± 52 ml −1 (0.5 h; P < 0.005) and 100 ± 37 ml −1 (4 h; P < 0.005), and from 216 ± 91 to 161 ± 50 ml −1 (0.5 h; P < 0.05) and 45 ± 23 ml −1 (4 h; P < 0.005), respectively. Upon return to normoxia, their concentration increased slowly, and after 4 h was still lower than at 0 h (P < 0.05). During hypoxia, CXCR-4 expression and plasmatic stromal derived cell factor-1 (SDF-1) increased abruptly (0.5 h: +126% and +13%, respectively; P < 0.05), suggesting cell marginalization as a possible cause of the rapid hypoxia-induced EPC reduction. Moreover, hypoxia exposure induced an increase in EPC apoptosis and markers of oxidative stress, which was significantly evident only starting from 2 h and 4 h after hypoxia offset, respectively, suggesting that EPC apoptosis may contribute to the later phase of hypoxia-induced EPC reduction. Overall, these observations may provide new insights into the understanding of the mechanisms operated by EPCs to maintain endothelial homeostasis.

Endothelial Progenitor Cell Homing Decreases Postoperative Complications in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

“…Our results are consistent with recent reports that acute injuries induced by S. typhus vaccination injection (28) or acute hypoxia (29) do not cause immediate mobilization of vascular progenitors.…”

Comparison of Fibronectin and Collagen in Supporting the Isolation and Expansion of Endothelial Progenitor Cells from Human Adult Peripheral Blood

“…Apart from these differences in cytokine production, our results clearly indicated that ECFCs expanded on fibronectin and collagen shared similar ability for in vitro tubulogenesis and similar phenotype. It is important to note that also CXCR4, receptor for stromal-derived cell factor-1 with a key role in selective migration and recruitment of endothelial progenitor cells into the sites of blood vessel formation and repair [14], [45], was similarly expressed on ECFCs cultured on the two substrates. This is a crucial issue, because ECFCs are increasingly used in studies of in vivo vasculogenesis, where the ability of these cells to adequately localize into the sites of tissue injury is indeed a crucial prerequisite.…”

“…EPCs have stimulated considerable interest in recent years due to the observation that variations in their number and function are associated with many pathological conditions, mainly cardiovascular diseases and cancer [6]–[12]. The behaviour of EPCs during particular physiologic challenges are under intense investigation as well, to better understand the role and function of these cells in human physiology [9], [13], [14]. Moreover, EPCs are being studied for their role in maintaining the integrity of endogenous endothelium and their regenerative potential, with studies indicating the beneficial effect of EPC-based cell therapies in both animal models and human diseases [15], [16].…”

Electroencephalogram (EEG) Alpha Power as a Marker of Visuospatial Attention Orienting and Suppression in Normoxia and Hypoxia. An Exploratory Study

“…Excess air flow was diverted outside the mask to prevent inspired oxygen pressure from increasing above 90 Torr (see Figure 2 for a visual exemplification). Since there are influential data in the physiological literature indicating that in humans the most relevant cardiorespiratory and blood plasmatic effects were found in between 2-4 h of serious hypoxic respiration (see, e.g., [46]), all our volunteers were systematically submitted to the EEG recording session starting after 2 h of such a respiratory condition, which was spent in the application and jellying of a 128 electrodes electrocap as well as in the filling of the mood and alert paper-and- Since there are influential data in the physiological literature indicating that in humans the most relevant cardiorespiratory and blood plasmatic effects were found in between 2-4 h of serious hypoxic respiration (see, e.g., [46]), all our volunteers were systematically submitted to the EEG recording session starting after 2 h of such a respiratory condition, which was spent in the application and jellying of a 128 electrodes electrocap as well as in the filling of the mood and alert paper-and-pencil scales, besides in an alert letter-cancellation-based task. For experimental standardization and session comparison-sake, the volunteers started their tasks-related EEG recordings after 2 h during the normoxic session too, a span of time overall spent in the activities mentioned above besides the electrocap application.…”