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Exposure to hypoxia, through ascension to high altitudes (HAs), air travel, or human disease, is associated with an increased incidence of thrombosis in some settings. Mechanisms underpinning this increased thrombosis risk remain incompletely understood, and the effects of more sustained hypoxia on the human platelet molecular signature and associated functional responses have never been examined. We examined the effects of prolonged (≥2 months continuously) hypobaric hypoxia on platelets isolated from subjects residing at HA (3,700 meters) and, for comparison, matched subjects residing under normoxia conditions at sea level (50 meters). Using complementary transcriptomic, proteomic, and functional methods, we identified that the human platelet transcriptome is markedly altered under prolonged exposure to hypobaric hypoxia at HA. Among the significantly, differentially expressed genes (mRNA and protein), were those having canonical roles in platelet activation and thrombosis, including membrane glycoproteins (e.g. GP4, GP6, GP9 ), integrin subunits (e.g. ITGA2B ), and alpha-granule chemokines (e.g. SELP, PF4V1 ). Platelets from subjects residing at HA were hyperactive, as demonstrated by increased engagement and adhesion to fibrinogen, fewer alpha granules by transmission electron microscopy, increased circulating PF4 and ADP, and significantly enhanced clot retraction. In conclusion, we identify that prolonged hypobaric hypoxia exposure due to HA alters the platelet transcriptome and proteome, triggering increased functional activation responses that may contribute to thrombosis. Our findings may also have relevance across a range of human diseases where chronic hypoxia, platelet activation, and thrombosis are increased.

Objective: To compare young males' sleep quality and structure between native Tibetans and longtime Han residents., Methods: A total of 14 male Tibetans and 11 male Hans at an altitude of 3 780 m were enrolled in this study. Tibetans were native highlanders with a mean age of (32.0 ± 9.1) years. Han subjects were born and living in high altitude with a mean age of (36.6 ± 7.6) years. All subjects were monitored by Polysomnography(PSG), and the differences of sleep structure and quality between the two groups were compared according to the international standard., Results: The sleep efficiency (93.1% ± 3.9% vs 85.7% ± 4.2%) and nocturnal oxygen saturation (SpO(2)) (89.4% ± 2.0% vs 84.6% ± 4.3%) in Tibetans was significantly higher than those in Hans (both P<0.05). The number of awakening ((1.9 ± 0.8) vs (4.1 ± 1.3)/h) and micro-awakening ((23.4 ± 5.8) vs (28.7 ± 4.1)/h), the oxygen reduction index ((11.7 ± 4.8) vs (16.3 ± 7.5)/h), apnea hypoventilation index (AHI) ((5.8 ± 2.3) vs (9.6 ± 4.2)/h) and average heart rate ((66.9 ± 8.3) vs (79.9 ± 6.7)/min) of Tibetans were significantly lower than Hans (all P<0.05). Tibetans had longer slow wave sleep (20.1% ± 7.2% vs 8.8% ± 3.3%) and the Hans had longer stage 2 of non-rapid eye movement (NREM) (31.1% ± 11.9% vs 18.4% ± 6.7%) and shallow sleep (76.1 ± 11.7 vs 70.8 ± 11.2) (all P<0.05)., Conclusion: Tibetans have better sleep quality and higher sleep efficiency than Han residents at high altitude.

Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.