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  • Title: Transcriptomic profiling reveals gene expression kinetics in patients with hypoxia and high altitude pulmonary edema.
    Author: Yuhong L, Tana W, Zhengzhong B, Feng T, Qin G, Yingzhong Y, Wei G, Yaping W, Langelier C, Rondina MT, Ge RL.
    Journal: Gene; 2018 Apr 20; 651():200-205. PubMed ID: 29366758.
    Abstract:
    OBJECTIVE: High altitude pulmonary edema (HAPE) is a life threatening condition occurring in otherwise healthy individuals who rapidly ascend to high altitude. However, the molecular mechanisms of its pathophysiology are not well understood. The objective of this study is to evaluate differential gene expression in patients with HAPE during acute illness and subsequent recovery. METHODS: Twenty-one individuals who ascended to an altitude of 3780 m were studied, including 12 patients who developed HAPE and 9 matched controls without HAPE. Whole-blood samples were collected during acute illness and subsequent recovery for analysis of the expression of hypoxia-related genes, and physiologic and laboratory parameters, including mean pulmonary arterial pressure (mPAP), heart rate, blood pressure, and arterial oxygen saturation (SpO2), were also measured. RESULTS: Compared with control subjects, numerous hypoxia-related genes were up-regulated in patients with acute HAPE. Gene network analyses suggested that HIF-1α played a central role in acute HAPE by affecting a variety of hypoxia-related genes, including BNIP3L, VEGFA, ANGPTL4 and EGLN1. Transcriptomic profiling revealed the expression of most HAPE-induced genes was restored to a normal level during the recovery phase except some key hypoxia response factors, such asBNIP3L, EGR1, MMP9 and VEGF, which remained persistently elevated. CONCLUSIONS: Differential expression analysis of hypoxia-related genes revealed distinct molecular signatures of HAPE during acute and recovery phases. This study may help us to better understand HAPE pathogenesis and putative targets for further investigation and therapeutic intervention.
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