Elevated pentose phosphate pathway is involved in the recovery of hypoxia-induced erythrocytosis

Abstract

As a typical model of hypoxia-induced excessive erythrocytosis, high altitude polycythemia (HAPC) results in microcirculation disturbance, aggravates tissue hypoxia and results in a severe clinical outcome, without any effective intervention methods except for returning to an oxygen-rich environment. The present study aimed to explore potential therapeutic targets which may participate in the recovery of HAPC by studying the mechanisms of reducing the hemoglobin (HB) concentration during re-oxygenation. A total of 14 and 13 subjects were recruited over a 5,300 m distance and 5,170 m area. The patients were classified into HAPC or control groups based on their HB value. Plasma samples were collected on the day when they finished their stay in plateau for a year, and on the 180th day following their reaching in plain. Metabolic profiling was conducted by UPLC-QTOF/MS. MetaboAnalyst platform was performed to explore the most perturbed metabolic pathways. A panel of differential metabolites were obtained in the recovery phase of HAPC and control groups. The present study identified the uniquely upregulated pentose phosphate pathway in HAPC subjects, along with a significantly decreased HB level. The findings were verified via a direct comparison between HAPC and control subjects at a high altitude. An increased pentose phosphate pathway was identified in control groups compared with HAPC subjects. An elevated pentose phosphate pathway may therefore participate in the recovery of HAPC, whereas a downregulated pentose phosphate pathway may contribute to hypoxia-induced erythrocytosis. The results of the present study provide potential therapeutic strategies and novel insights into the pathogenesis of hypoxia-induced polycythemia.

Correlation between RBC changes and coagulation parameters in high altitude population

“…It was reported that staying at HA may increase the risk of thrombotic diseases. Hypoxia may induce significant changes of the factors which contribute to thrombosis, such as blood pressure elevation, increase of RBC, HGB and HCT levels, prolongation of PT and APTT, decrease of PLT count and et al [3,4,[13][14][15]. However, it is still unclear that whether these factors are interrelated.…”

“…It was reported that in response to the insufficient amount of oxygen, HGB and HCT levels significantly increased at HA. The increased HGB is potentially important for improving the oxygen-carrying capacity of RBCs, meanwhile significantly increased HCT values will lead to hyperviscosity and lower blood flow velocity which may augment clinical risks of thrombosis [2][3][4][12][13][14]. Thus, the effects of HGB and HCT on coagulation parameters may be different.…”

“…It was reported that over 140 million people worldwide permanently live at altitudes >2500 m above sea level. Low ambient temperature and hypobaric hypoxia are two challenges to life at high altitude (HA) [1,2], with an increased risk of thrombotic diseases following prolonged stay at HA [3][4][5][6]. The environmental conditions in HA affect the morphology and phenotype of blood cells [3].…”

“…Red blood cell (RBC) count, hemoglobin (HGB) concentrations and hematocrit (HCT) would reach a fairly high level in most of the individuals following long-term exposure to HA situations. Moreover, excessive erythropoiesis, higher HCT and overburdened HGB will lead to hyperviscosity [3,4,[7][8][9].…”

Redox–Oligomeric State of Peroxiredoxin-2 and Glyceraldehyde-3-Phosphate Dehydrogenase in Obstructive Sleep Apnea Red Blood Cells under Positive Airway Pressure Therapy

“…Hypoxia favors glycolysis and downregulates PPP, which impairs the capacities of RBC to cope with oxidative stress and ultimately its ability to carrying oxygen to tissues [36,37]. A study performed in high-altitude polycythemia (HAPC) subjects, a typical model of hypoxia-induced excessive erythrocytosis (increased RBC production to maintain the oxygen level in the body), demonstrated that the PPP metabolic pathway was decreased in these subjects compared to controls but increased after reoxygenation recovery at plain altitude, along with a significant decrease in the RBC and Hb level [38]. OSA is characterized by intermittent hypoxemia/reoxygenation events leading to oxidative stress [39].…”