Hypoxia: Adapting to High Altitude by Mutating EPAS-1 , the Gene Encoding HIF-2α

Tissot van Patot, Martha C.; Gassmann, Max

doi:10.1089/ham.2010.1099

Cited by 119High Altitude and HypoxiaCancer, Hypoxia, and MetabolismErythropoietin and Anemia Treatment

Hypoxia: Adapting to High Altitude by Mutating EPAS-1 , the Gene Encoding HIF-2α

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Tissot van Patot, Martha C., Gassmann, Max·2011·High Altitude Medicine & Biology

DOI 10.1089/ham.2010.1099

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Abstract

Living at high altitude is demanding and thus drives adaptational mechanisms. The Tibetan population has had a longer evolutionary period to adapt to high altitude than other mountain populations such as Andeans. As a result, some Tibetans living at high altitudes do not show markedly elevated red blood cell production as compared to South American high altitude natives such as Quechuas or Aymaras, thereby avoiding high blood viscosity creating cardiovascular risk. Unexpectedly, the responsible mutation(s) reducing red blood cell production do not involve either the gene encoding the blood hormone erythropoietin (Epo), or the corresponding regulatory sequences flanking the Epo gene. Similarly, functional mutations in the hypoxia-inducible transcription factor 1α (HIF-1α) gene that represents the oxygen-dependent subunit of the HIF-1 heterodimer, the latter being the main regulator of over 100 hypoxia-inducible genes, have not been described so far. It was not until very recently that three independent groups showed that the gene encoding HIF-2α, EPAS-1 (Wenger et al. 1997), represents a key gene mutated in Tibetan populations adapted to living at high altitudes (Beall et al. 2010 , Yi et al. 2010 , Simonson et al. 2010). Hypoxia-inducible transcription factors were first identified by the description of HIF-1 (Semenza et al. 1991 , 1992), which was subsequently found to enhance transcription of multiple genes that encode proteins necessary for rescuing from hypoxic exposure, including erythropoietic, angiogenic and glycolytic proteins. Then HIF-2 was identified (Ema et al. 1997 ; Flamme et al. 1997 ; Hogenesch et al. 1997 ; and Tian et al. 1997) and although it is highly similar to HIF-1 and has the potential to bind (Camenisch et al. 2001) and mediate (Mole et al. 2009) many of the same genes as HIF-1, its biological actions in response to hypoxia are distinct from those of HIF-1 (reviewed by Loboda et al. 2010). By now, several of these HIF-2 mediated processes have been implicated in the human response to high altitude exposure including erythropoiesis (Kapitsinou et al. 2010), iron homeostasis (Peyssonnaux et al. 2008), metabolism (Shohet et al. 2007; Tormos et al. 2010; Biswas et al. 2010 ; Rankin et al. 2009) and vascular permeability (Chen et al. 2009; Tanaka et al. 2005), among others. Clearly, mutation of EPAS-1 has the potential to bring far more advantage when adapting to high altitude than solely mutating the Epo gene.

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Men and women have different hemoglobin reference ranges yet similar EPO levels.
“This new equilibrium set point for EPO/hemoglobin has precedent in the observation that men and women have different hemoglobin reference ranges yet similar EPO levels (42).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [42]
Genetic variations in HIF2A, PHD2 and PPARA associate with lower hemoglobins in native Tibetans compared to Han Chinese and with high altitude adaptation in other populations.
“Genome-wide searches for single-nucleotide polymorphisms (SNP), candidate gene approaches and exome sequencing have identified genetic variations in the HIF2A, PHD2 and PPARA genes that associate with lower hemoglobins in native Tibetans compared to Han Chinese and with high altitude adaptation in other populations.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [180]

Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981 · see citing works
A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617 · see citing works
Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude
Yi, X., Liang, Y., Huerta-Sanchez, E., Jin, X., Cuo, Z. X. P., Pool, J. E., Xu, X., Jiang, H., Vinckenbosch, N., Korneliussen, T. S., et al. (2010) · Science · doi:10.1126/science.1190371 · Cited by 1,611 · cited 4× · see citing works
“This makes the current reports of mutated EPAS-1 in the Tibetan population unique in the fact that these mutations are associated with loss of function or low hemoglobin concentrations in healthy individuals described very recently (Yi et al. 2010; Beall et al. 2010; Bigham et al. 2009).”
Influential
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386 · see citing works
Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells.
Tian, H., McKnight, S. L., & Russell, D. W. (1997) · Genes & Development · doi:10.1101/gad.11.1.72 · Cited by 1,351 · see citing works
Genetic Evidence for High-Altitude Adaptation in Tibet
Simonson, T. S., Yang, Y., Huff, C. D., Yun, H., Qin, G., Witherspoon, D. J., Bai, Z., Lorenzo, F. R., Xing, J., Jorde, L. B., et al. (2010) · Science · doi:10.1126/science.1189406 · Cited by 1,227 · see citing works
Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor
Appelhoff, R. J., Tian, Y.-M., Raval, R. R., Turley, H., Harris, A. L., Pugh, C. W., Ratcliffe, P. J., & Gleadle, J. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406026200 · Cited by 1,108 · see citing works
A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development
Ema, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., & Fujii-Kuriyama, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4273 · Cited by 1,016 · see citing works
Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.
Semenza, G. L., Nejfelt, M. K., Chi, S. M., & Antonarakis, S. E. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.13.5680 · Cited by 990 · see citing works
Natural selection on EPAS1 ( HIF2α ) associated with low hemoglobin concentration in Tibetan highlanders
Beall, C. M., Cavalleri, G. L., Deng, L., Elston, R. C., Gao, Y., Knight, J., Li, C., Li, J. C., Liang, Y., McCormack, M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002443107 · Cited by 845 · see citing works
Loss of HIF-2α and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice
Compernolle, V., Brusselmans, K., Acker, T., Hoet, P., Tjwa, M., Beck, H., Plaisance, S., Dor, Y., Keshet, E., Lupu, F., et al. (2002) · Nature Medicine · doi:10.1038/nm721 · Cited by 733 · see citing works
Identification of a Natural Soluble Form of the Vascular Endothelial Growth Factor Receptor, FLT-1, and Its Heterodimerization with KDR
Kendall, R. L., Wang, G., & Thomas, K. A. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1355 · Cited by 730 · see citing works
The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development
Tian, H., Hammer, R. E., Matsumoto, A. M., Russell, D. W., & McKnight, S. L. (1998) · Genes & Development · doi:10.1101/gad.12.21.3320 · Cited by 647 · see citing works
Consensus Statement on Chronic and Subacute High Altitude Diseases
Lèon‐Velarde, F., Maggiorini, M., Reeves, J. Τ., Aldashev, A. A., Asmus, I., Bernardi, L., Ge, R.-L., Hackett, P. H., Kobayashi, T., MOORE, L. G., et al. (2005) · High Altitude Medicine & Biology · doi:10.1089/ham.2005.6.147 · Cited by 629 · see citing works
Erythropoietin Gene Expression in Human, Monkey and Murine Brain
Marti, H. H., Wenger, R. H., Rivas, L. A., Straumann, U., Oigicaylioglu, M., Henn, V. S., Yonekawa, Y., Bauer, C., & Gassmann, M. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01252.x · Cited by 553 · see citing works
Self-citation
Genome-wide Association of Hypoxia-inducible Factor (HIF)-1α and HIF-2α DNA Binding with Expression Profiling of Hypoxia-inducible Transcripts
Mole, D. R., Blancher, C., Copley, R. R., Pollard, P. J., Gleadle, J. M., Ragoussis, J., & Ratcliffe, P. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m901790200 · Cited by 552 · see citing works
HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration
Grimm, C., Wenzel, A., Groszer, M., Mayser, H., Seeliger, M. W., Samardzija, M., Bauer, C., Gassmann, M., & Remé, C. E. (2002) · Nature Medicine · doi:10.1038/nm723 · Cited by 517 · see citing works
Self-citation
Characterization of a Subset of the Basic-Helix-Loop-Helix-PAS Superfamily That Interacts with Components of the Dioxin Signaling Pathway
Hogenesch, J. B., Chan, W. K., Jackiw, V., Brown, R. C., Gu, Y.-Z., Pray-Grant, M. G., Perdew, G. H., & Bradfield, C. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8581 · Cited by 514 · see citing works
Oxygen(es) and the hypoxia-inducible factor-1.
Wenger, R. H., & Gassmann, M. (1997) · PubMed · Cited by 513 · see citing works
Self-citation
HIF-2α, but not HIF-1α, promotes iron absorption in mice
Mastrogiannaki, M., Matak, P., Keith, B., Simon, M. C., Vaulont, S., & Peyssonnaux, C. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38499 · Cited by 502 · see citing works
Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1−/− mice.
Scortegagna, M., Ding, K., Oktay, Y., Gaur, A., Thurmond, F., Yan, L.-J., Marck, B. T., Matsumoto, A. M., Shelton, J. M., Richardson, J. A., et al. (2003) · Nature Genetics · doi:10.1038/ng1266 · Cited by 496 · see citing works
Localization of specific erythropoietin binding sites in defined areas of the mouse brain.
Digicaylioglu, M. H., Bichet, S., Marti, H. H., et al. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.9.3717 · Cited by 480 · see citing works
HIF-1 and HIF-2 Transcription Factors - Similar but Not Identical
Loboda, A., Jozkowicz, A., & Dulak, J. (2010) · Molecules and Cells · doi:10.1007/s10059-010-0067-2 · Cited by 477 · see citing works
High-Altitude Pulmonary Edema Is Initially Caused by an Increase in Capillary Pressure
Maggiorini, M., Mélot, C., Pierre, S., et al. (2001) · Circulation · doi:10.1161/01.cir.103.16.2078 · Cited by 472 · see citing works
Regulation of Hypoxia-Inducible Factor 2α Signaling by the Stress-Responsive Deacetylase Sirtuin 1
Dioum, E. M., Chen, R., Alexander, M. S., Zhang, Q., Hogg, R. T., Gerard, R. D., & Garcia, J. A. (2009) · Science · doi:10.1126/science.1169956 · Cited by 470 · see citing works
The transcription factor EPAS-1/hypoxia-inducible factor 2α plays an important role in vascular remodeling
Peng, J., Zhang, L., Drysdale, L., & Fong, G.-H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.140087397 · Cited by 460 · cited 1× · see citing works
“Mutating EPAS-1 in mice and cells Initial attempts to knock out EPAS-1 in mice resulted in embryonic lethality due to inhibition of catecholamine activation in mid-gestation (Tian et al. 1998) and impaired angiogenesis (Peng et al. 2000).”
Intestinal Hypoxia-Inducible Transcription Factors Are Essential for Iron Absorption following Iron Deficiency
Shah, Y. M., Matsubara, T., Ito, S., Yim, S.-H., & Gonzalez, F. J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.012 · Cited by 431 · see citing works
Physiological adaptation to high altitude: oxygen transport in mammals and birds
Monge, C., & Lèon‐Velarde, F. (1991) · Physiological Reviews · doi:10.1152/physrev.1991.71.4.1135 · Cited by 396 · see citing works
Differentiating the functional role of hypoxia‐inducible factor (HIF)‐1α and HIF‐2α (EPAS‐1) by the use of RNA interference: erythropoietin is a HIF‐2α target gene in Hep3B and Kelly cells
Warnecke, C., Zaborowska, Z., Kurreck, J., Erdmann, V. A., Frei, U. A., Wiesener, M. S., & Eckardt, K. (2004) · The FASEB Journal · doi:10.1096/fj.04-1640fje · Cited by 395 · see citing works
Frataxin Acts as an Iron Chaperone Protein to Modulate Mitochondrial Aconitase Activity
Bulteau, A.-L., O’Neill, H. A., Kennedy, M. C., Ikeda‐Saito, M., Isaya, G., & Szweda, L. I. (2004) · Science · doi:10.1126/science.1098991 · Cited by 372 · see citing works
Humoral Regulation of Red Cell Production
Erslev, A. J. (1953) · Blood · doi:10.1182/blood.v8.4.349.349 · Cited by 367 · see citing works
HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1α and developmentally expressed in blood vessels
Flamme, I., Fröhlich, T., von Reutern, M., Kappel, A., Damert, A., & Risau, W. (1997) · Mechanisms of Development · doi:10.1016/s0925-4773(97)00674-6 · Cited by 366 · see citing works
The N-Terminal Transactivation Domain Confers Target Gene Specificity of Hypoxia-inducible Factors HIF-1α and HIF-2α
Hu, C.-J., Sataur, A., Wang, L., Chen, H., & Simon, M. C. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-05-0419 · Cited by 355 · see citing works
High Altitude Cerebral Edema
Hackett, P. H., & Roach, R. C. (2004) · High Altitude Medicine & Biology · doi:10.1089/1527029041352054 · Cited by 351 · see citing works
The Hypoxia-Associated Factor Switches Cells from HIF-1α- to HIF-2α-Dependent Signaling Promoting Stem Cell Characteristics, Aggressive Tumor Growth and Invasion
Koh, M. Y., Lemos, R., Liu, X., & Powis, G. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4142 · Cited by 350 · see citing works
Signalling hypoxia by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.08.111 · Cited by 343 · see citing works
Physiological aspects of high-altitude pulmonary edema
Bärtsch, P., Mairbäurl, H., Maggiorini, M., et al. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01167.2004 · Cited by 341 · see citing works
Hypoxia-inducible factor 2 regulates hepatic lipid metabolism
Rankin, E. B., Rha, J., Selak, M. A., Unger, T. L., Keith, B., Liu, Q., & Haase, V. H. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00200-09 · Cited by 338 · see citing works
Response of Skeletal Muscle Mitochondria to Hypoxia
Hoppeler, H. H., Vogt, M., Weibel, E. R., & Flück, M. (2003) · Experimental Physiology · doi:10.1113/eph8802513 · Cited by 329 · see citing works
Biology of hypoxia-inducible factor-2α in development and disease
Patel, S. A., & Simon, M. C. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.17 · Cited by 325 · see citing works
Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia
Fang, H.-Y., Hughes, R., Murdoch, C., Coffelt, S. B., Biswas, S. K., Harris, A. L., Johnson, R. S., Imityaz, H. Z., Simon, M. C., Fredlund, E., et al. (2009) · Blood · doi:10.1182/blood-2008-12-195941 · Cited by 319 · see citing works
Heterozygous deficiency of hypoxia-inducible factor–2α protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia
Brusselmans, K., Compernolle, V., Tjwa, M., Wiesener, M. S., Maxwell, P. H., Collen, D., & Carmeliet, P. (2003) · Journal of Clinical Investigation · doi:10.1172/jci15496 · Cited by 316 · see citing works
A Gain-of-Function Mutation in the HIF2A Gene in Familial Erythrocytosis
Percy, M. J., Furlow, P. W., Lucas, G. S., Li, X., Lappin, T. R. J., McMullin, M. F., & Lee, F. S. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa073123 · Cited by 314 · cited 4× · see citing works
“…of recent data demonstrating genetic variation in EPAS-1 resulting in phenotypic differences (Yi et al. 2010; Beall et al. 2010; Bigham et al. 2009; Percy et al. 2008), it is possible that the gene encoding HIF-1 a gene was replicated at some point in evolution giving rise to EPAS-1 and HIF-2 a .”
Influential
Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia
Kapitsinou, P. P., Liu, Q., Unger, T. L., Rha, J., Davidoff, O., Keith, B., Epstein, J. A., Moores, S. L., Erickson-Miller, C. L., & Haase, V. H. (2010) · Blood · doi:10.1182/blood-2010-02-270322 · Cited by 307 · see citing works
Cooperative Interaction of Hypoxia-inducible Factor-2α (HIF-2α) and Ets-1 in the Transcriptional Activation of Vascular Endothelial Growth Factor Receptor-2 (Flk-1)
Elvert, G., Kappel, A., Heidenreich, R., Englmeier, U., Lanz, S., Acker, T., Rauter, M., Plate, K. H., Sieweke, M. H., Breier, G., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211298200 · Cited by 272 · see citing works
Evidence for the functional activity of hypoxia-inducible transcription factors overexpressed in preeclamptic placentae
Rajakumar, A., Brandon, H. M., Daftary, A., Ness, R., & Conrad, K. P. (2004) · Placenta · doi:10.1016/j.placenta.2004.02.011 · Cited by 251 · see citing works
Pulmonary nitric oxide in mountain dwellers
Beall, C. M., Laskowski, D. M., Strohl, K. P., Soria, R., Villena, M., Vargas, E., Alarcon, A. M., Gonzales, C., & ERZURUM, S. C. (2001) · Nature · doi:10.1038/35106641 · Cited by 242 · see citing works
The Transcriptional Activator Hypoxia Inducible Factor 2 (HIF-2/EPAS-1) Regulates the Oxygen-Dependent Expression of Erythropoietin in Cortical Astrocytes
Chavez, J. C., Baranova, O. V., Lin, J. C.-H., & Pichiule, P. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2838-06.2006 · Cited by 240 · see citing works
Cobalt promotes angiogenesis via hypoxia-inducible factor and protects tubulointerstitium in the remnant kidney model
Tanaka, T., Kojima, I., Ohse, T., Ingelfinger, J. R., Adler, S., Fujita, T., & Nangaku, M. (2005) · Laboratory Investigation · doi:10.1038/labinvest.3700328 · Cited by 238 · see citing works
HLF/HIF‐2α is a key factor in retinopathy of prematurity in association with erythropoietin
Morita, M., Ohneda, O., Yamashita, T., Takahashi, S., Suzuki, N., Nakajima, O., Kawauchi, S., Ema, M., Shibahara, S., Udono, T., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg117 · Cited by 230 · see citing works
Regulating cellular oxygen sensing by hydroxylation
Fandrey, J., Gorr, T. A., & Gassmann, M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.05.005 · Cited by 229 · see citing works
Self-citation
Identifying positive selection candidate loci for high-altitude adaptation in Andean populations
Bigham, A. W., Mao, X., Mei, R., Brutsaert, T. D., Wilson, M. J., Julian, C. G., Parra, E. J., Akey, J. M., MOORE, L. G., & Shriver, M. D. (2009) · Human Genomics · doi:10.1186/1479-7364-4-2-79 · Cited by 219 · see citing works
Role of the hypoxia inducible factors HIF in iron metabolism
Peyssonnaux, C., Nizet, V., & Johnson, R. S. (2008) · Cell Cycle · doi:10.4161/cc.7.1.5145 · Cited by 217 · see citing works
A Gene Encoding Antigenic Peptides of Human Squamous Cell Carcinoma Recognized by Cytotoxic T Lymphocytes
Shichijo, S., Nakao, M., Imai, Y., Takasu, H., Kawamoto, M., Niiya, F., Yang, D., Toh, Y., Yamana, H., & Itoh, K. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.3.277 · Cited by 214 · see citing works
Identification of Hypoxia-response Element in the Human Endothelial Nitric-oxide Synthase Gene Promoter
Coulet, F., Nadaud, S., Agrapart, M., & Soubrier, F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305420200 · Cited by 203 · see citing works
The lung at high altitude: bronchoalveolar lavage in acute mountain sickness and pulmonary edema
Schoene, R. B., Swenson, E. R., Pizzo, C. J., et al. (1988) · Journal of Applied Physiology · doi:10.1152/jappl.1988.64.6.2605 · Cited by 193 · see citing works
Small-molecule inhibitors of HIF-2a translation link its 5'UTR iron-responsive element to oxygen sensing
Zimmer, M., Ebert, B. L., Neil, C., Brenner, K., Papaioannou, I., Melas, A., Tolliday, N., Lamb, J., Pantopoulos, K., Golub, T., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.12.004 · Cited by 191 · see citing works
Arterial catecholamine responses during exercise with acute and chronic high-altitude exposure
Mazzeo, R. S., Bender, P. R., Brooks, G. A., Butterfield, G. E., Groves, B. Μ., Sutton, J. R., Wolfel, E. E., & Reeves, J. Τ. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.261.4.e419 · Cited by 187 · see citing works
p38 MAP Kinase—a molecular switch between VEGF‐induced angiogenesis and vascular hyperpermeability
Bieber, K., Marti, H. H., Hippenstiel, S., Springmann, G., Voswinckel, R., Gaumann, A. K. A., Breier, G., Drexler, H. C. A., Suttorp, N., & Clauss, M. A. (2002) · The FASEB Journal · doi:10.1096/fj.02-0329fje · Cited by 179 · see citing works
Magnetic Resonance Imaging Evidence of Cytotoxic Cerebral Edema in Acute Mountain Sickness
Kallenberg, K., Bailey, D. M., Christ, S., Mohr, A., Roukens, R., Menold, E., Steiner, T., Bärtsch, P., & Knauth, M. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600404 · Cited by 178 · see citing works
The Human Hypoxia-Inducible Factor 1α Gene:HIF1AStructure and Evolutionary Conservation
Iyer, N. V., Leung, S. W., & Semenza, G. L. (1998) · Genomics · doi:10.1006/geno.1998.5416 · Cited by 176 · see citing works
The Polycythemia of High Altitudes: Iron Metabolism and Related Aspects
REYNAFARJE, C., Lozano, R., & Valdivieso, J. (1959) · Blood · doi:10.1182/blood.v14.4.433.433 · Cited by 172 · see citing works
Hypoxia and angiogenesis: regulation of hypoxia-inducible factors via novel binding factors
Chen, L., Endler, A., & Shibasaki, F. (2009) · Experimental & Molecular Medicine · doi:10.3858/emm.2009.41.12.103 · Cited by 164 · see citing works
Different hematologic responses to hypoxia in Sherpas and Quechua Indians
Winslow, R. M., Chapman, K. W., Gibson, C. C., Samaja, M., Monge, C., Goldwasser, E., SHERPA, M. T., Blume, F. D., & Raimundo Santolaya, C. (1989) · Journal of Applied Physiology · doi:10.1152/jappl.1989.66.4.1561 · Cited by 160 · see citing works
Autosomal dominant erythrocytosis and pulmonary arterial hypertension associated with an activating HIF2α mutation
Gale, D. P., Harten, S. K., Reid, C. D. L., Tuddenham, E. G. D., & Maxwell, P. H. (2008) · Blood · doi:10.1182/blood-2008-04-153718 · Cited by 157 · see citing works
Role of ETS Transcription Factors in the Hypoxia-Inducible Factor-2 Target Gene Selection
Aprelikova, O. N., Wood, M. J. A., Tackett, S. A., Chandramouli, G. V. R., & Barrett, J. C. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3345 · Cited by 156 · see citing works
Increased Cerebral Infarct Volumes in Polyglobulic Mice Overexpressing Erythropoietin
Wießner, C., ALLEGRINI, P. R., Ekatodramis, D., Jewell, U. R., Stallmach, T., & Gassmann, M. (2001) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200107000-00011 · Cited by 154 · see citing works
Self-citation
Child health and living at high altitude
Niermeyer, S., Mollinedo, P. A., & Huicho, L. (2008) · Archives of Disease in Childhood · doi:10.1136/adc.2008.141838 · Cited by 150 · see citing works
A Humoral Mechanism in Anoxic Erythrocytosis
BONSDORFF, E., & JALAVISTO, E. (1948) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1948.tb00535.x · Cited by 146 · see citing works
Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies
Soliz, J., Joseph, V., Soulage, C. O., Becskei, C., Vogel, J., Péquignot, J.-M., Ogunshola, O. O., & Gassmann, M. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.093328 · Cited by 142 · see citing works
Self-citation
Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle
Robach, P., Cairo, G., Gelfi, C., Bernuzzi, F., Pilegaard, H., Viganò, A., Santambrogio, P., Cerretelli, P., Calbet, J. A. L., Moutereau, S., et al. (2007) · Blood · doi:10.1182/blood-2006-08-040006 · Cited by 141 · see citing works
The Translation Initiation Factor eIF3-p48 Subunit Is Encoded byint-6, a Site of Frequent Integration by the Mouse Mammary Tumor Virus Genome
Asano, K., Merrick, W. C., & Hershey, J. W. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23477 · Cited by 140 · see citing works
Free Radical-Mediated Damage to Barrier Function is not Associated with Altered Brain Morphology in High-Altitude Headache
Bailey, D. M., Roukens, R., Knauth, M., Kallenberg, K., Christ, S., Mohr, A., Genius, J., Storch-Hagenlocher, B., Meisel, F., McEneny, J., et al. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600169 · Cited by 131 · see citing works
Non-Erythroid Functions of Erythropoietin
Gassmann, M., Heinicke, K., Soliz, J., et al. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-8997-0_22 · Cited by 128 · see citing works
Self-citation
Effects of hypobaric hypoxia on the fetoplacental unit: The morphometric diffusing capacity of the villous membrane at high altitude
Reshetnikova, O. S., Burton, G. J., & Milovanov, A. P. (1994) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(94)90402-2 · Cited by 127 · see citing works
Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis
Percy, M. J., Beer, P. A., Campbell, G., Dekker, A. W., Green, A. R., Oscier, D., Rainey, M. G., van Wijk, R., Wood, M., Lappin, T. R. J., et al. (2008) · Blood · doi:10.1182/blood-2008-02-137703 · Cited by 127 · see citing works
Keeping the engine primed: HIF factors as key regulators of cardiac metabolism and angiogenesis during ischemia
Shohet, R. V., & Garcia, J. A. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0279-x · Cited by 127 · see citing works
Proteins modulation in human skeletal muscle in the early phase of adaptation to hypobaric hypoxia
Viganò, A., Ripamonti, M., Palma, S. D., Capitanio, D., Vasso, M., Wait, R., Lundby, C., Cerretelli, P., & Gelfi, C. (2008) · PROTEOMICS · doi:10.1002/pmic.200800232 · Cited by 126 · see citing works
Protective Role of Hypoxia-Inducible Factor-2α against Ischemic Damage and Oxidative Stress in the Kidney
Kojima, I., Tanaka, T., Inagi, R., Kato, H., Yamashita, T., Sakiyama, A., Ohneda, O., Takeda, N., Sata, M., Miyata, T., et al. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006060639 · Cited by 122 · see citing works
High-altitude pulmonary hypertension: a pathophysiological entity to different diseases
Maggiorini, M., & Lèon‐Velarde, F. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00052403 · Cited by 115 · see citing works
Effect of Altitude on Erythropoiesis
Faura, J., RAMOS, J., REYNAFARJE, C., English, E., Finne, P. H., & Finch, C. A. (1969) · Blood · doi:10.1182/blood.v33.5.668.668 · Cited by 114 · see citing works
Hypoxic Ventilatory Response, Ventilation, Gas Exchange, and Fluid Balance in Acute Mountain Sickness
Bärtsch, P., Swenson, E. R., Paul, A., et al. (2002) · High Altitude Medicine & Biology · doi:10.1089/15270290260512846 · Cited by 112 · see citing works
Increased cerebral output of free radicals during hypoxia: implications for acute mountain sickness?
Bailey, D. M., Taudorf, S., Berg, R. M. G., Lundby, C., McEneny, J., Young, I. S., Evans, K. A., James, P. E., Shore, A., Hullin, D. A., et al. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00366.2009 · Cited by 109 · see citing works
Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning
Tissot van Patot, M. C., Murray, A. J., Beckey, V., Cindrova-Davies, T., Johns, J., Zwerdlinger, L., Jauniaux, E., Burton, G. J., & Serkova, N. J. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00383.2009 · Cited by 107 · see citing works
Microbial and Immunological Responses Relative to High-Altitude Exposure in Mountaineers
Kleessen, B., Schroedl, W., Stueck, M., Richter, A. A., RIECK, O., & Krueger, M. (2005) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000174888.22930.e0 · Cited by 104 · see citing works
Chronic Mountain Sickness and the Heart
Lèon‐Velarde, F., Villafuerte, F. C., & Richalet, J. (2010) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2010.02.012 · Cited by 100 · see citing works
Greater free plasma VEGF and lower soluble VEGF receptor-1 in acute mountain sickness
van Patot, M. C. T., Leadbetter, G., Keyes, L. E., Bendrick‐Peart, J., Beckey, V. E., Christians, U., & Hackett, P. H. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00589.2004 · Cited by 100 · see citing works
The influence of high-altitude living on body iron
Cook, J. D., Boy, E., Flowers, C. W., & Daroca, M. D. C. (2005) · Blood · doi:10.1182/blood-2004-12-4782 · Cited by 98 · see citing works
Hypoxia-inducible Factor 2α Regulates Expression of the Mitochondrial Aconitase Chaperone Protein Frataxin
Oktay, Y., Dioum, E. M., Matsuzaki, S., Ding, K., Yan, L., Haller, R. G., Szweda, L. I., & Garcia, J. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611133200 · Cited by 92 · see citing works
The Hypoxia-Inducible Factor-2α Is Stabilized by Oxidative Stress Involving NOX4
Diebold, I., Flügel, D., Becht, S., BelAiba, R. S., Bonello, S., Hess, J., Kietzmann, T., & Görlach, A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.3014 · Cited by 92 · see citing works
Effects of HIF-1 and HIF2 on Growth and Metabolism of Clear-Cell Renal Cell Carcinoma 786-0 Xenografts
Biswas, S., Troy, H., Leek, R., Chung, Y.-L., Li, J.-L., Raval, R. R., Turley, H., Gatter, K., Pezzella, F., Griffiths, J. R., et al. (2010) · Journal of Oncology · doi:10.1155/2010/757908 · Cited by 89 · see citing works
Acclimatization to 4100 m does not change capillary density or mRNA expression of potential angiogenesis regulatory factors in human skeletal muscle
Lundby, C., Pilegaard, H., Andersen, J. L., van Hall, G., Sander, M., & Calbet, J. A. L. (2004) · Journal of Experimental Biology · doi:10.1242/jeb.01225 · Cited by 85 · see citing works
Effects of high-altitude exposure on vascular endothelial growth factor levels in man
Walter, R. B., Maggiorini, M., Scherrer, U., et al. (2001) · European Journal of Applied Physiology · doi:10.1007/s004210100419 · Cited by 79 · see citing works
Improved lung growth and function through hypoxia‐inducible factor in primate chronic lung disease of prematurity
Asikainen, T. M., Chang, L.-Y., Coalson, J. J., Schneider, B. K., Waleh, N. S., Ikegami, M., Shannon, J. M., Winter, V. T., Grubb, P. H., Clyman, R. I., et al. (2006) · The FASEB Journal · doi:10.1096/fj.06-5887fje · Cited by 79 · see citing works
Inter‐connection between mitochondria and HIFs
Tormos, K. V., & Chandel, N. S. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01031.x · Cited by 75 · see citing works
The role of hypoxia-inducible transcription factors in the hypoxic neonatal brain
Trollmann, R., & Gassmann, M. (2009) · Brain and Development · doi:10.1016/j.braindev.2009.03.007 · Cited by 75 · see citing works
Self-citation
Activity of Hypoxia-inducible Factor 2α Is Regulated by Association with the NF-κB Essential Modulator
Bracken, C. P., Whitelaw, M. L., & Peet, D. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m409987200 · Cited by 73 · see citing works
A novel heterozygous HIF2AM535I mutation reinforces the role of oxygen sensing pathway disturbances in the pathogenesis of familial erythrocytosis
Martini, M., Teofili, L., Cenci, T., Giona, F., Torti, L., Rea, M., Foa, R., Leone, G., & Larocca, L. M. (2008) · Haematologica · doi:10.3324/haematol.13210 · Cited by 73 · see citing works
Attenuation of HIF-1 DNA-binding activity limits hypoxia-inducible endothelin-1 expression
Camenisch, G., Stroka, D., Gassmann, M., & Wenger, R. H. (2001) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240100679 · Cited by 72 · see citing works
Self-citation
Weekly iron supplementation is as effective as 5 day per week iron supplementation in Bolivian school children living at high altitude
Berger, J., Aguayo, V., Téllez, W., Lujan, C., Traissac, P., & Miguel, J. S. (1997) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1600418 · Cited by 72 · see citing works
Body Temperature, Autonomic Responses, and Acute Mountain Sickness
Loeppky, J. A., Icenogle, M. V., Maes, D., Riboni, K., Scotto, P., & Roach, R. C. (2003) · High Altitude Medicine & Biology · doi:10.1089/152702903769192322 · Cited by 70 · see citing works
Developmental responses to high altitude hypoxia
Frisancho, A. R. (1970) · American Journal of Physical Anthropology · doi:10.1002/ajpa.1330320310 · Cited by 69 · see citing works
Viral respiratory infection increases susceptibility of young rats to hypoxia-induced pulmonary edema
Carpenter, T. C., Reeves, J. Τ., & Durmowicz, A. G. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.84.3.1048 · Cited by 69 · see citing works
Early erythropoietin, blood, and physiological responses to severe hypoxia in man.
Siri, W. E., Dyke, D. C. V., Winchell, H. S., Pollycove, M., Parker, H. G., & Cleveland, A. S. (1966) · Journal of Applied Physiology · doi:10.1152/jappl.1966.21.1.73 · Cited by 69 · see citing works
A hypoxia complement differentiates the muscle response to endurance exercise
Schmutz, S., Däpp, C., Wittwer, M., Durieux, A., Müeller, M., Weinstein, F. V., Vogt, M., Hoppeler, H. H., & Flück, M. (2010) · Experimental Physiology · doi:10.1113/expphysiol.2009.051029 · Cited by 66 · see citing works
Mammalian Tumor Suppressor Int6 Specifically Targets Hypoxia Inducible Factor 2α for Degradation by Hypoxia- and pVHL-independent Regulation
Chen, L., Uchida, K., Endler, A., & Shibasaki, F. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700423200 · Cited by 66 · see citing works
Plasma Vascular Endothelial Growth Factor in Acute Mountain Sickness
Maloney, J. P., Wang, D., Duncan, T., et al. (2000) · CHEST Journal · doi:10.1378/chest.118.1.47 · Cited by 62 · see citing works
Hypoxia-Induced Mitogenic Factor Has Antiapoptotic Action and Is Upregulated in the Developing Lung
Wagner, K. F., Hellberg, A.-K., Balenger, S. L., Depping, R., Dodd‐o, J. M., Johns, R. A., & Li, D. (2004) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2003-0319oc · Cited by 57 · see citing works
High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men
Gonzales, G. F., Gasco, M., Tapia, V., & Gonzales-Castañeda, C. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90940.2008 · Cited by 51 · see citing works
Soluble Vascular Endothelial Growth Factor Receptor 1 Inhibits Edema and Epithelial Proliferation Induced by 17β-Estradiol in the Mouse Uterus
Hastings, J. M., Licence, D. R., Burton, G. J., et al. (2002) · Endocrinology · doi:10.1210/en.2002-220641 · Cited by 51 · see citing works
Hypoxic ventilatory response and acute mountain sickness
Milledge, J., Thomas, P., Beeley, J. M., et al. (1988) · European Respiratory Journal · doi:10.1183/09031936.93.01100948 · Cited by 47 · see citing works
Impact of Pregnancy at High Altitude on Placental Morphology in Non-native Women With and Without Preeclampsia
van Patot, M. C. T., Valdez, M., Becky, V., Cindrová‐Davies, T., Johns, J., Zwerdling, L., Jauniaux, E. R. M., & Burton, G. J. (2009) · Placenta · doi:10.1016/j.placenta.2009.04.002 · Cited by 42 · see citing works
Acute and chronic exposure to hypoxia alters ventilatory pattern but not minute ventilation of mice overexpressing erythropoietin
Soliz, J., Soulage, C. O., Hermann, D. M., et al. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00350.2007 · Cited by 42 · see citing works
Mitochondrial reactive oxygen species are required for hypoxia‐induced degradation of keratin intermediate filaments
Na, N., Chandel, N. S., Litvan, J., & Ridge, K. M. (2009) · The FASEB Journal · doi:10.1096/fj.08-128967 · Cited by 42 · see citing works
The Connectivity Map Links Iron Regulatory Protein-1–Mediated Inhibition of Hypoxia-Inducible Factor-2a Translation to the Anti-inflammatory 15-deoxy-Δ12,14-Prostaglandin J2
Zimmer, M., Lamb, J., Ebert, B. L., Lynch, M. C., Neil, C. R., Schmidt, E. V., Golub, T. R., & Iliopoulos, O. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2877 · Cited by 40 · see citing works
Respiratory and Circulatory Control at High Altitudes
West, J. B. (1982) · Journal of Experimental Biology · doi:10.1242/jeb.100.1.147 · Cited by 39 · see citing works
Correlated response, competition, and female canine size in primates
Plavcan, J. M. (1998) · American Journal of Physical Anthropology · doi:10.1002/(sici)1096-8644(199812)107:4 · Cited by 39 · see citing works
Hypoxia inducible factor (HIF)‐2α is required for the development of the catecholaminergic phenotype of sympathoadrenal cells
Brown, S. T., Kelly, K. F., Daniel, J. M., & Nurse, C. A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06153.x · Cited by 38 · see citing works
Erythrocytosis associated with a novel missense mutation in the HIF2A gene
van Wijk, R., Sutherland, S., Van Wesel, A. C. W., Huizinga, E. G., Percy, M. J., Bierings, M., & Lee, F. S. (2010) · Haematologica · doi:10.3324/haematol.2009.017582 · Cited by 38 · see citing works
Erythropoietin Levels in Lowlanders and High-Altitude Natives at 3450 m
Basu, M., Malhotra, A. S., Pal, K., et al. (2007) · Aviation Space and Environmental Medicine · doi:10.3357/asem.2085.2007 · Cited by 37 · see citing works
The Neuronal Control of Hypoxic Ventilation
Gassmann, M., van Patot, M. C. T., & Soliz, J. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05028.x · Cited by 36 · see citing works
Self-citation
Note on the composition of alveolar air at extreme heights
Somervell, T. H. (1925) · The Journal of Physiology · doi:10.1113/jphysiol.1925.sp002246 · Cited by 35 · see citing works
Role of Hypoxia-Inducible Transcription Factors 1α and 2α in the Regulation of Plasminogen Activator Inhibitor-1 Expression in a Human Trophoblast Cell Line
Meade, E., Ma, Y., & Guller, S. M. (2007) · Placenta · doi:10.1016/j.placenta.2007.04.005 · Cited by 35 · see citing works
Digoxin, HIF-1, and cancer
Lopez-Lazaro, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813047106 · Cited by 32 · see citing works
A Variant of the Endothelial Nitric Oxide Synthase Gene ( NOS3 ) Associated with AMS Susceptibility Is Less Common in the Quechua, a High Altitude Native Population
Wang, P., Ha, A. Y. N., Kídd, K. K., et al. (2010) · High Altitude Medicine & Biology · doi:10.1089/ham.2009.1054 · Cited by 32 · see citing works
Genetic adaptation to extreme hypoxia:
Lorenzo, F., Yang, Y., Simonson, T. S., Nussenzveig, R. H., Jorde, L. B., Prchal, J. T., & Ge, R. (2009) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2009.04.006 · Cited by 31 · see citing works
Effects of exposure to a simulated altitude of 5500 m on energy metabolic pathways in rats
Ou, L. C., & Leiter, J. C. (2004) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2004.04.001 · Cited by 30 · see citing works
Placental HIFs as markers of cerebral hypoxic distress in fetal mice
Trollmann, R., Strasser, K., Keller, S., Antoniou, X., Grenacher, B., Ogunshola, O. O., Dötsch, J., Rascher, W., & Gassmann, M. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00053.2008 · Cited by 26 · see citing works
Self-citation
High-altitude acclimation increases the triacylglycerol/fatty acid cycle at rest and during exercise
McClelland, G. B., Hochachka, P. W., Reidy, S. P., & Weber, J. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.3.e537 · Cited by 26 · see citing works
Metabolic Markers of Hypoxia: Systems Biology Application in Biomedicine
Serkova, N. J., Reisdorph, N. A., & van Patot, M. C. T. (2008) · Toxicology Mechanisms and Methods · doi:10.1080/15376510701795769 · Cited by 25 · see citing works
PULMONARY VASCULAR PATHOLOGY OF HIGH ALTITUDE-INDUCED PULMONARY HYPERTENSION IN CATTLE.
Alexander, A. F., & JENSEN, R. (1963) · PubMed · Cited by 22 · see citing works
Ventilatory responses to acute and chronic hypoxia are altered in female but not male Paskin-deficient mice
Soliz, J., Soulage, C. O., Borter, E., van Patot, M. C. T., & Gassmann, M. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00876.2007 · Cited by 20 · see citing works
Self-citation
Altitude-related illness in children
Carpenter, T. C., Niermeyer, S., & Durmowicz, A. G. (1998) · Current Problems in Pediatrics · doi:10.1016/s0045-9380(98)80066-2 · Cited by 20 · see citing works
Role of Epidermal Growth Factor Receptor in Ovine Fetal Pulmonary Vascular Remodeling Following Exposure to High Altitude Long-Term Hypoxia
Sheng, L., Zhou, W., Hislop, A. A., Ibe, B. O., Longo, L. D., & Raj, J. U. (2008) · High Altitude Medicine & Biology · doi:10.1089/ham.2008.1034 · Cited by 17 · see citing works
Familial erythrocytosis arising from a gain-of-function mutation in the HIF2A gene of the oxygen sensing pathway.
Percy, M. J. (2008) · PubMed Central · Cited by 11 · see citing works
Evaluation of iron stores as limiting high altitude polycythemia
Hornbein, T. F. (1962) · Journal of Applied Physiology · doi:10.1152/jappl.1962.17.2.243 · Cited by 11 · see citing works
Impaired Cardiopulmonary Transition at High Altitude † 1710
Niermeyer, S., Shaffer, E., & MOORE, L. G. (1998) · Pediatric Research · doi:10.1203/00006450-199804001-01732 · Cited by 9 · see citing works

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Bachman, E., Travison, T. G., Basaria, S., Davda, M. N., Guo, W., Li, M., Connor Westfall, J., Bae, H., Gordeuk, V., & Bhasin, S. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glt154 · Cited by 426 · see citing works
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Ayalew, W., Xiaoyun, W., Tarekegn, G. M., Tessema, T. S., Chu, M., Liang, C., Naboulsi, R., Van Damme, R., Bongcam-Rudloff, E., & Ping, Y. (2024) · BMC Genomics · doi:10.1186/s12864-024-10936-5 · Cited by 15 · see citing works

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Conley, D. J., Carstensen, J., Aigars, J., Axe, P. G., Bonsdorff, E., Eremina, T. R., Haahti, B.-M., Humborg, C., Jonsson, P. R., Kotta, J., et al. (2011) · Environmental Science & Technology · doi:10.1021/es201212r · Cited by 510 · see citing works
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Long, W. C., & Seitz, R. D. (2009) · Estuaries and Coasts · doi:10.1007/s12237-009-9132-5 · Cited by 31 · see citing works
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Blaszczak, J. R., Koenig, L., Mejia, F. H., Gómez‐Gener, L., Dutton, C. L., Carter, A. M., Grimm, N. B., Harvey, J. W., Helton, A. M., & Cohen, M. J. (2022) · Limnology and Oceanography Letters · doi:10.1002/lol2.10297 · Cited by 95 · see citing works

Authors: Tissot van Patot, M. C., & Gassmann, M.
Affiliations: Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland.
University of Zurich (CH)
ORCID: Gassmann, Max
Venue: High Altitude Medicine & Biology
Publisher: SAGE Publications
Published: 2011-06
Volume: 12
Issue: 2
Pages: 157-167
ISSN: 1527-0297 (ISSN-L)
1557-8682
DOI: 10.1089/ham.2010.1099
OpenAlex: W2010389102
Cited by: 119
References: 137
Citations by year: 2026: 6 · 2025: 9 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 11 · 2019: 3 · 2018: 3 · 2017: 8 · 2016: 12 · 2015: 7 · 2014: 7 · 2013: 16 · 2012: 8
FWCI: 6.57
Type: journal article
Language: en
Open access: green
doi.org
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations: High Altitude Medicine & Biology (publishedVersion)
PubMed (publishedVersion)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Zurich Open Repository and Archive (University of Zurich)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Keywords: HIF-2α, high-altitude adaptation, Tibetan population, hypoxia, erythropoiesis, HIF-1α, erythropoietin, hypoxia-inducible factor, hypoxia-responsive genes, Andean peoples, blood viscosity, cardiovascular risk, genetic mutations
MeSH terms: Endothelial PAS Domain-Containing Protein 1, Adaptation, Biological, Altitude, Hypoxia, Erythropoiesis, Erythropoietin, Humans, Mutation, Tibet, Asian People, Basic Helix-Loop-Helix Proteins

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Hypoxia: Adapting to High Altitude by Mutating EPAS-1 , the Gene Encoding HIF-2α

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