References:
Abe K, Shinoda M, Tanaka M, Kuwabara Y, Yoshida K, Hirooka Y, et
al. (2016). Haemodynamic unloading reverses occlusive vascular lesions
in severe pulmonary hypertension. Cardiovasc Res 111: 16-25.
Ball MK, Waypa GB, Mungai PT, Nielsen JM, Czech L, Dudley VJ, et
al. (2014). Regulation of hypoxia-induced pulmonary hypertension by
vascular smooth muscle hypoxia-inducible factor-1alpha. Am J Respir Crit
Care Med 189: 314-324.
Barnes EA, Chen CH, Sedan O, & Cornfield DN (2017). Loss of smooth
muscle cell hypoxia inducible factor-1alpha underlies increased vascular
contractility in pulmonary hypertension. FASEB J 31: 650-662.
Beall CM, Cavalleri GL, Deng L, Elston RC, Gao Y, Knight J, et
al. (2010). Natural selection on EPAS1 (HIF2alpha) associated with low
hemoglobin concentration in Tibetan highlanders. Proc Natl Acad Sci U S
A 107: 11459-11464.
Bigham A, Bauchet M, Pinto D, Mao X, Akey JM, Mei R, et al.(2010). Identifying signatures of natural selection in Tibetan and
Andean populations using dense genome scan data. PLoS Genet 6:e1001116.
Bigham AW, & Lee FS (2014). Human high-altitude adaptation: forward
genetics meets the HIF pathway. Genes Dev 28: 2189-2204.
Bigham AW, Wilson MJ, Julian CG, Kiyamu M, Vargas E, Leon-Velarde
F, et al. (2013). Andean and Tibetan patterns of adaptation to
high altitude. Am J Hum Biol 25: 190-197.
Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Thebaud B,
Bonnet S, et al. (2006). An abnormal mitochondrial-hypoxia
inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and
triggers pulmonary arterial hypertension in fawn hooded rats:
similarities to human pulmonary arterial hypertension. Circulation
113: 2630-2641.
Bracken CP, Fedele AO, Linke S, Balrak W, Lisy K, Whitelaw ML, et
al. (2006). Cell-specific regulation of hypoxia-inducible factor
(HIF)-1alpha and HIF-2alpha stabilization and transactivation in a
graded oxygen environment. J Biol Chem 281: 22575-22585.
Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen
D, et al. (2003). Heterozygous deficiency of hypoxia-inducible
factor-2alpha protects mice against pulmonary hypertension and right
ventricular dysfunction during prolonged hypoxia. J Clin Invest
111: 1519-1527.
Brutsaert TD, Kiyamu M, Elias Revollendo G, Isherwood JL, Lee FS,
Rivera-Ch M, et al. (2019). Association of EGLN1 gene with high
aerobic capacity of Peruvian Quechua at high altitude. Proc Natl Acad
Sci U S A 116: 24006-24011.
Chen W, Hill H, Christie A, Kim MS, Holloman E, Pavia-Jimenez A,
et al. (2016). Targeting renal cell carcinoma with a HIF-2 antagonist.
Nature 539: 112-117.
Cho H, Du X, Rizzi JP, Liberzon E, Chakraborty AA, Gao W, et al.(2016). On-target efficacy of a HIF-2alpha antagonist in preclinical
kidney cancer models. Nature 539: 107-111.
Coleman ML, McDonough MA, Hewitson KS, Coles C, Mecinovic J, Edelmann
M, et al. (2007). Asparaginyl hydroxylation of the Notch ankyrin
repeat domain by factor inhibiting hypoxia-inducible factor. J Biol Chem
282: 24027-24038.
Courtney KD, Infante JR, Lam ET, Figlin RA, Rini BI, Brugarolas J,
et al. (2018). Phase I Dose-Escalation Trial of PT2385, a
First-in-Class Hypoxia-Inducible Factor-2alpha Antagonist in Patients
With Previously Treated Advanced Clear Cell Renal Cell Carcinoma. J Clin
Oncol 36: 867-874.
Cowburn AS, Crosby A, Macias D, Branco C, Colaco RD, Southwood M,
et al. (2016). HIF2alpha-arginase axis is essential for the development
of pulmonary hypertension. Proc Natl Acad Sci U S A 113:8801-8806.
Dai Z, Li M, Wharton J, Zhu MM, & Zhao YY (2016). Prolyl-4 Hydroxylase
2 (PHD2) Deficiency in Endothelial Cells and Hematopoietic Cells Induces
Obliterative Vascular Remodeling and Severe Pulmonary Arterial
Hypertension in Mice and Humans Through Hypoxia-Inducible Factor-2alpha.
Circulation 133: 2447-2458.
Dai Z, Zhu MM, Peng Y, Machireddy N, Evans CE, Machado R, et al.(2018). Therapeutic Targeting of Vascular Remodeling and Right Heart
Failure in Pulmonary Arterial Hypertension with a HIF-2alpha Inhibitor.
Am J Respir Crit Care Med 198: 1423-1434.
Deng Z, Haghighi F, Helleby L, Vanterpool K, Horn EM, Barst RJ, et
al. (2000). Fine mapping of PPH1, a gene for familial primary pulmonary
hypertension, to a 3-cM region on chromosome 2q33. Am J Respir Crit Care
Med 161: 1055-1059.
Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, & Zeiher AM
(1999). Activation of nitric oxide synthase in endothelial cells by
Akt-dependent phosphorylation. Nature 399: 601-605.
Dunham-Snary KJ, Wu D, Sykes EA, Thakrar A, Parlow LRG, Mewburn
JD, et al. (2017). Hypoxic Pulmonary Vasoconstriction: From
Molecular Mechanisms to Medicine. Chest 151: 181-192.
Euler USV LG (1946). Observations on the pulmonary arterial blood
pressure in the cat. Acta Physiol Scand 12: 301-320.
Formenti F, Beer PA, Croft QP, Dorrington KL, Gale DP, Lappin TR,
et al. (2011). Cardiopulmonary function in two human disorders of the
hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and
HIF-2alpha gain-of-function mutation. FASEB J 25: 2001-2011.
Fukuroda T, Ozaki S, Ihara M, Ishikawa K, Yano M, & Nishikibe M (1994).
Synergistic inhibition by BQ-123 and BQ-788 of endothelin-1-induced
contractions of the rabbit pulmonary artery. Br J Pharmacol
113: 336-338.
Gassmann M, Mairbaurl H, Livshits L, Seide S, Hackbusch M, Malczyk
M, et al. (2019). The increase in hemoglobin concentration with
altitude varies among human populations. Ann N Y Acad Sci 1450:204-220.
Groves BM, Droma T, Sutton JR, McCullough RG, McCullough RE, Zhuang
J, et al. (1993). Minimal hypoxic pulmonary hypertension in
normal Tibetans at 3,658 m. J Appl Physiol (1985) 74: 312-318.
Gupta ML, Rao KS, Anand IS, Banerjee AK, & Boparai MS (1992). Lack of
smooth muscle in the small pulmonary arteries of the native Ladakhi. Is
the Himalayan highlander adapted? Am Rev Respir Dis 145:1201-1204.
He X, Song S, Ayon RJ, Balisterieri A, Black SM, Makino A, et al.(2018). Hypoxia selectively upregulates cation channels and increases
cytosolic [Ca(2+)] in pulmonary, but not coronary, arterial smooth
muscle cells. Am J Physiol Cell Physiol 314: C504-C517.
Hickey MM, Richardson T, Wang T, Mosqueira M, Arguiri E, Yu H, et
al. (2010). The von Hippel-Lindau Chuvash mutation promotes pulmonary
hypertension and fibrosis in mice. J Clin Invest 120: 827-839.
Hirsila M, Koivunen P, Gunzler V, Kivirikko KI, & Myllyharju J (2003).
Characterization of the human prolyl 4-hydroxylases that modify the
hypoxia-inducible factor. J Biol Chem 278: 30772-30780.
Hopfl G, Ogunshola O, & Gassmann M (2003). Hypoxia and high altitude.
The molecular response. Adv Exp Med Biol 543: 89-115.
Horscroft JA, Kotwica AO, Laner V, West JA, Hennis PJ, Levett DZH,
et al. (2017). Metabolic basis to Sherpa altitude adaptation. Proc Natl
Acad Sci U S A 114: 6382-6387.
Hu CJ, Poth JM, Zhang H, Flockton A, Laux A, Kumar S, et al.(2019). Suppression of HIF2 signalling attenuates the initiation of
hypoxia-induced pulmonary hypertension. Eur Respir J.
International PPHC, Lane KB, Machado RD, Pauciulo MW, Thomson JR,
Phillips JA, 3rd, et al. (2000). Heterozygous germline mutations
in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary
hypertension. Nat Genet 26: 81-84.
Jewell UR, Kvietikova I, Scheid A, Bauer C, Wenger RH, & Gassmann M
(2001). Induction of HIF-1alpha in response to hypoxia is instantaneous.
FASEB J 15: 1312-1314.
Julian CG, & Moore LG (2019). Human Genetic Adaptation to High
Altitude: Evidence from the Andes. Genes (Basel) 10.
Kaelin WG, Jr., & Ratcliffe PJ (2008). Oxygen sensing by metazoans: the
central role of the HIF hydroxylase pathway. Mol Cell 30:393-402.
Kapitsinou PP, Rajendran G, Astleford L, Michael M, Schonfeld MP, Fields
T, et al. (2016). The Endothelial Prolyl-4-Hydroxylase Domain
2/Hypoxia-Inducible Factor 2 Axis Regulates Pulmonary Artery Pressure in
Mice. Mol Cell Biol 36: 1584-1594.
Kuhr FK, Smith KA, Song MY, Levitan I, & Yuan JX (2012). New mechanisms
of pulmonary arterial hypertension: role of Ca(2)(+) signaling. Am J
Physiol Heart Circ Physiol 302: H1546-1562.
Lorenzo FR, Huff C, Myllymäki M, Olenchock B, Swierczek S, Tashi
T, et al. (2014). A genetic mechanism for Tibetan high-altitude
adaptation. Nature genetics 46: 951.
Luks AM, & Swenson ER (2015). Evaluating the Risks of High Altitude
Travel in Chronic Liver Disease Patients. High Alt Med Biol 16:80-88.
Mauban JR, Remillard CV, & Yuan JX (2005). Hypoxic pulmonary
vasoconstriction: role of ion channels. J Appl Physiol (1985)
98: 415-420.
Moore LG, Niermeyer S, & Zamudio S (1998). Human adaptation to high
altitude: regional and life-cycle perspectives. Am J Phys Anthropol
Suppl 27: 25-64.
Penaloza D, & Arias-Stella J (2007a). The heart and pulmonary
circulation at high altitudes - Healthy highlanders and chronic mountain
sickness. Circulation 115: 1132-1146.
Penaloza D, & Arias-Stella J (2007b). The heart and pulmonary
circulation at high altitudes: healthy highlanders and chronic mountain
sickness. Circulation 115: 1132-1146.
Peng Y, Cui C, He Y, Ouzhuluobu, Zhang H, Yang D, et al. (2017).
Down-Regulation of EPAS1 Transcription and Genetic Adaptation of
Tibetans to High-Altitude Hypoxia. Mol Biol Evol 34: 818-830.
Peng YJ, Nanduri J, Khan SA, Yuan G, Wang N, Kinsman B, et al.(2011). Hypoxia-inducible factor 2alpha (HIF-2alpha) heterozygous-null
mice exhibit exaggerated carotid body sensitivity to hypoxia, breathing
instability, and hypertension. Proc Natl Acad Sci U S A 108:3065-3070.
Petousi N, Croft QP, Cavalleri GL, Cheng HY, Formenti F, Ishida K,
et al. (2014). Tibetans living at sea level have a hyporesponsive
hypoxia-inducible factor system and blunted physiological responses to
hypoxia. J Appl Physiol (1985) 116: 893-904.
Sakao S, Tatsumi K, & Voelkel NF (2009). Endothelial cells and
pulmonary arterial hypertension: apoptosis, proliferation, interaction
and transdifferentiation. Respir Res 10: 95.
Scheuermann TH, Tomchick DR, Machius M, Guo Y, Bruick RK, & Gardner KH
(2009). Artificial ligand binding within the HIF2alpha PAS-B domain of
the HIF2 transcription factor. Proc Natl Acad Sci U S A 106:450-455.
Schofield CJ, & Ratcliffe PJ (2004). Oxygen sensing by HIF
hydroxylases. Nat Rev Mol Cell Biol 5: 343-354.
Semenza GL (2012). Hypoxia-inducible factors in physiology and medicine.
Cell 148: 399-408.
Shimoda LA, Manalo DJ, Sham JS, Semenza GL, & Sylvester JT (2001).
Partial HIF-1alpha deficiency impairs pulmonary arterial myocyte
electrophysiological responses to hypoxia. Am J Physiol Lung Cell Mol
Physiol 281: L202-208.
Simonson TS, Yang Y, Huff CD, Yun H, Qin G, Witherspoon DJ, et
al. (2010). Genetic evidence for high-altitude adaptation in Tibet.
Science 329: 72-75.
Song S, Carr SG, McDermott KM, Rodriguez M, Babicheva A, Balistrieri
A, et al. (2018). STIM2 (Stromal Interaction Molecule 2)-Mediated
Increase in Resting Cytosolic Free Ca(2+) Concentration Stimulates PASMC
Proliferation in Pulmonary Arterial Hypertension. Hypertension
71: 518-529.
Soria R, Egger M, Scherrer U, Bender N, & Rimoldi SF (2016). Pulmonary
artery pressure and arterial oxygen saturation in people living at high
or low altitude: systematic review and meta-analysis. Journal of Applied
Physiology 121: 1151-1159.
Southgate L, Machado RD, Graf S, & Morrell NW (2020). Molecular genetic
framework underlying pulmonary arterial hypertension. Nat Rev Cardiol
17: 85-95.
Stenmark KR, Fasules J, Hyde DM, Voelkel NF, Henson J, Tucker A,
et al. (1987). Severe pulmonary hypertension and arterial adventitial
changes in newborn calves at 4,300 m. J Appl Physiol (1985) 62:821-830.
Sylvester JT, Shimoda LA, Aaronson PI, & Ward JP (2012). Hypoxic
pulmonary vasoconstriction. Physiol Rev 92: 367-520.
Tan Q, Kerestes H, Percy MJ, Pietrofesa R, Chen L, Khurana TS, et
al. (2013). Erythrocytosis and pulmonary hypertension in a mouse model
of human HIF2A gain of function mutation. J Biol Chem 288:17134-17144.
Tang H, Babicheva A, McDermott KM, Gu Y, Ayon RJ, Song S, et al.(2018). Endothelial HIF-2alpha contributes to severe pulmonary
hypertension due to endothelial-to-mesenchymal transition. Am J Physiol
Lung Cell Mol Physiol 314: L256-L275.
Tian H, McKnight SL, & Russell DW (1997). Endothelial PAS domain
protein 1 (EPAS1), a transcription factor selectively expressed in
endothelial cells. Genes Dev 11: 72-82.
Wallace EM, Rizzi JP, Han G, Wehn PM, Cao Z, Du X, et al. (2016).
A Small-Molecule Antagonist of HIF2alpha Is Efficacious in Preclinical
Models of Renal Cell Carcinoma. Cancer Res 76: 5491-5500.
Wang B, Zhang YB, Zhang F, Lin H, Wang X, Wan N, et al. (2011).
On the origin of Tibetans and their genetic basis in adapting
high-altitude environments. PLoS One 6: e17002.
Wang GL, Jiang BH, Rue EA, & Semenza GL (1995). Hypoxia-inducible
factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by
cellular O2 tension. Proc Natl Acad Sci U S A 92: 5510-5514.
Wang J, Weigand L, Lu W, Sylvester JT, Semenza GL, & Shimoda LA (2006).
Hypoxia inducible factor 1 mediates hypoxia-induced TRPC expression and
elevated intracellular Ca2+ in pulmonary arterial smooth muscle cells.
Circ Res 98: 1528-1537.
Wehn PM, Rizzi JP, Dixon DD, Grina JA, Schlachter ST, Wang B, et
al. (2018). Design and Activity of Specific Hypoxia-Inducible
Factor-2alpha (HIF-2alpha) Inhibitors for the Treatment of Clear Cell
Renal Cell Carcinoma: Discovery of Clinical Candidate (
S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1
H-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385). J Med Chem 61:9691-9721.
Wilkins MR, Aldashev AA, Wharton J, Rhodes CJ, Vandrovcova J,
Kasperaviciute D, et al. (2014). α1-A680T variant in GUCY1A3 as a
candidate conferring protection from pulmonary hypertension among Kyrgyz
highlanders. Circulation: Cardiovascular Genetics 7: 920-929.
Wilkins MR, Ghofrani HA, Weissmann N, Aldashev A, & Zhao L (2015).
Pathophysiology and treatment of high-altitude pulmonary vascular
disease. Circulation 131: 582-590.
Witt KE, & Huerta-Sanchez E (2019). Convergent evolution in human and
domesticate adaptation to high-altitude environments. Philos Trans R Soc
Lond B Biol Sci 374: 20180235.
Xiang K, Ouzhuluobu, Peng Y, Yang Z, Zhang X, Cui C, et al.(2013). Identification of a Tibetan-specific mutation in the hypoxic
gene EGLN1 and its contribution to high-altitude adaptation. Mol Biol
Evol 30: 1889-1898.
Xu S, Li S, Yang Y, Tan J, Lou H, Jin W, et al. (2011). A
genome-wide search for signals of high-altitude adaptation in Tibetans.
Mol Biol Evol 28: 1003-1011.
Xu X, Tan X, Tampe B, Sanchez E, Zeisberg M, & Zeisberg EM (2015).
Snail Is a Direct Target of Hypoxia-inducible Factor 1alpha (HIF1alpha)
in Hypoxia-induced Endothelial to Mesenchymal Transition of Human
Coronary Endothelial Cells. J Biol Chem 290: 16653-16664.
Yan Q, Bartz S, Mao M, Li L, & Kaelin WG, Jr. (2007). The
hypoxia-inducible factor 2alpha N-terminal and C-terminal
transactivation domains cooperate to promote renal tumorigenesis in
vivo. Mol Cell Biol 27: 2092-2102.
Yang J, Jin Z-B, Chen J, Huang X-F, Li X-M, Liang Y-B, et al.(2017). Genetic signatures of high-altitude adaptation in Tibetans.
Proceedings of the National Academy of Sciences 114: 4189-4194.
Yi X, Liang Y, Huerta-Sanchez E, Jin X, Cuo ZX, Pool JE, et al.(2010). Sequencing of 50 human exomes reveals adaptation to high
altitude. Science 329: 75-78.
Young JM, Williams DR, & Thompson AAR (2019). Thin Air, Thick Vessels:
Historical and Current Perspectives on Hypoxic Pulmonary Hypertension.
Front Med (Lausanne) 6: 93.
Zhao L, Oliver E, Maratou K, Atanur SS, Dubois OD, Cotroneo E, et
al. (2015). The zinc transporter ZIP12 regulates the pulmonary vascular
response to chronic hypoxia. Nature 524: 356-360.
Zhu N, Pauciulo MW, Welch CL, Lutz KA, Coleman AW, Gonzaga-Jauregui
C, et al. (2019). Novel risk genes and mechanisms implicated by
exome sequencing of 2572 individuals with pulmonary arterial
hypertension. Genome Med 11: 69.
Zimmer M, Ebert BL, Neil C, Brenner K, Papaioannou I, Melas A, et
al. (2008). Small-molecule inhibitors of HIF-2a translation link its
5’UTR iron-responsive element to oxygen sensing. Mol Cell 32:838-848.