Hoffmann F, Limper U, Zaha VG, Reuter H, Zange L, Schulz-Menger J,...& Tank J (2020) Evolution of pulmonary hypertension during severe sustained hypoxia. Circulation, 141(18), 1504–1506.
Tuder RM, Archer SL, Dorfmüller P, Erzurum SC, Guignabert C, Michelakis E,...& Morrell NW (2013) Relevant issues in the pathology and pathobiology of pulmonary hypertension. J Am College Cardiol, 62(25S), D4-D12.
Thenappan T, Ormiston ML, Ryan JJ, & Archer SL (2018) Pulmonary arterial hypertension: pathogenesis and clinical management. Bmj, 360.
CaroJ S. Hypoxia-inducible factor1alpha (HIF-1 [alpha] lpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-inducud changes. J Biol Chem. 1997;272:22642–7.
Seagroves TN, Ryan HE, Lu H, Wouters BG, Knapp M, Thibault P,...& Johnson RS (2001) Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells. Molecular and cellular biology, 21(10), 3436–3444.
Bushuev VI, Miasnikova GY, Sergueeva AI, Polyakova LA, Okhotin D, Gaskin PR,...& Gordeuk VR (2006) Endothelin-1, vascular endothelial growth factor and systolic pulmonary artery pressure in patients with Chuvash polycythemia. Haematologica, 91(6), 744–749.
Formenti F, Beer PA, Croft QP, Dorrington KL, Gale DP, Lappin TR,...& Robbins PA (2011) Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2α gain-of-function mutation. The FASEB Journal, 25(6), 2001.
Gale DP, Harten SK, Reid CD, Tuddenham EG, Maxwell PH. Autosomal dominant erythrocytosis and pulmonary arterial hypertension associated with an activating HIF2 α mutation. Blood, J Am Soc Hematol. 2008;112(3):919–21.
Brusselmans K, Compernolle V, Tjwa M, Wiesener MS, Maxwell PH, Collen D, Carmeliet P. Heterozygous deficiency of hypoxia-inducible factor–2α protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J Clin Investig. 2003;111(10):1519–27.
Article CAS PubMed PubMed Central Google Scholar
Ahmad A, Ahmad S, Malcolm KC, Miller SM, Hendry-Hofer T, Schaack JB, White CW. Differential regulation of pulmonary vascular cell growth by hypoxia-inducible transcription factor–1α and hypoxia-inducible transcription factor–2α. Am J Respir Cell Mol Biol. 2013;49(1):78–85.
Article CAS PubMed PubMed Central Google Scholar
Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y. 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. Proc Natl Acad Sci. 1997;94(9):4273–8.
Article CAS PubMed PubMed Central Google Scholar
Cowburn AS, Crosby A, Macias D, Branco C, Colaço RD, Southwood M,...& Johnson RS (2016) HIF2α–arginase axis is essential for the development of pulmonary hypertension. Proc Natl Acad Sci, 113(31), 8801–8806.
Chan DC. Mitochondrial dynamics and its involvement in disease. Annu Rev Pathol. 2020;15:235–59.
Article CAS PubMed Google Scholar
Jin JY, Wei XX, Zhi XL, Wang XH, Meng D. Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin. 2021;42(5):655–64.
Article CAS PubMed Google Scholar
Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Thébaud B, Bonnet S,...& Archer SL (2006) An abnormal mitochondrial–hypoxia inducible factor-1α–Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation, 113(22), 2630–2641.
Archer SL, Gomberg-Maitland M, Maitland ML, Rich S, Garcia JG, Weir EK. Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1α-Kv1. 5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol-Heart Circ Physiol. 2008;294(2):570–8.
Sanderson SM, Locasale JW. Revisiting the Warburg effect: some tumors hold their breath. Cell Metab. 2018;28(5):669–70.
Article CAS PubMed PubMed Central Google Scholar
Chen Z, Liu M, Li L, Chen L. Involvement of the Warburg effect in non-tumor diseases processes. J Cell Physiol. 2018;233(4):2839–49.
Article CAS PubMed Google Scholar
Stephens OR, Weiss K, Frimel M, Rose JA, Sun Y, Asosingh K,...& Erzurum SC (2019) Interdependence of hypoxia and β-adrenergic receptor signaling in pulmonary arterial hypertension. Am J Physiol-Lung Cell Mol Physiol, 317(3), L369-L380.
Kwon B. Regulation of inflammation by bidirectional signaling through CD137 and its ligand. Immune Network. 2012;12(5):176–80.
Article PubMed PubMed Central Google Scholar
Teijeira A, Labiano S, Garasa S, Etxeberria I, Santamaría E, Rouzaut A,...& Melero I (2018) Mitochondrial morphological and functional reprogramming following CD137 (4–1BB) costimulation. Cancer immunol Res, 6(7), 798–811.
Xu Y, Zhang Y, Xu Y, Zang G, Li B, Xia H, Yuan W. Activation of CD137 signaling promotes macrophage apoptosis dependent on p38 MAPK pathway-mediated mitochondrial fission. Int J Biochem Cell Biol. 2021;136:106003.
Article CAS PubMed Google Scholar
Xu Y, Chen R, Yan J, Zang G, Shao C, Wang Z. CD137 Signal Mediates Cardiac Ischemia-Reperfusion Injury by Regulating the Necrosis of Cardiomyocytes. J Cardiovasc Transl Res. 2022;15:1163–75.
Lu Y, Li C, Du S, Chen X, Zeng X, Liu F,...& Chen J (2018) 4–1BB signaling promotes alveolar macrophages-mediated pro-fibrotic responses and crystalline silica-induced pulmonary fibrosis in mice. Front Immunol, 9, 1848.
Jeon HJ, Choi JH, Jung IH, Park JG, Lee MR, Lee MN,...& Oh GT (2010) CD137 (4–1BB) deficiency reduces atherosclerosis in hyperlipidemic mice. Circulation, 121(9), 1124–1133.
Melero I, Sanmamed MF, Glez-Vaz J, Luri-Rey C, Wang J, Chen L. CD137 (4–1BB)-Based cancer immunotherapy on its 25th anniversary. Cancer Discov. 2023;13(3):552–69.
Article CAS PubMed Google Scholar
Drenkard D, Becke FM, Langstein J, Spruss T, Kunz‐Schughart LA, Tan TE,...& Schwarz H (2007) CD137 is expressed on blood vessel walls at sites of inflammation and enhances monocyte migratory activity. FASEB J, 21(2), 456–463.
Yuan W, Xu C, Li B, Xia H, Pan Y, Zhong W,...& Wang B (2021) Contributions of costimulatory molecule CD137 in endothelial cells. J Am Heart Assoc, 10(11), e020721.
Palazón A, Martínez-Forero I, Teijeira A, Morales-Kastresana A, Alfaro C, Sanmamed MF,...& Melero I (2012) The HIF-1α hypoxia response in tumor-infiltrating T lymphocytes induces functional CD137 (4–1BB) for immunotherapy. Cancer Dis, 2(7), 608–623.
Labiano S, Palazón A, Bolanos E, Azpilikueta A, Sánchez-Paulete AR, Morales-Kastresana A,...& Melero I (2016) Hypoxia-induced soluble CD137 in malignant cells blocks CD137L-costimulation as an immune escape mechanism. Oncoimmunology, 5(1), e1062967.
Prchal JT, Gordeuk VR. HIF-2 inhibitor, erythrocytosis, and pulmonary hypertension. Blood. 2021;137(18):2424–5.
Article CAS PubMed Google Scholar
Shimoda LA. What’s HIF got to do with it? HIF-2 inhibition and pulmonary hypertension. Am J Respir Crit Care Med. 2018;198(11):1363–5.
Waypa GB, Schumacker PT (2019) Roles of HIF1 and HIF2 in pulmonary hypertension: it all depends on the context. Eur Respir J, 54(6),1901929.
Hu CJ, Poth JM, Zhang H, et al. Suppression of HIF2 signalling attenuates the initiation of hypoxia-induced pulmonary hypertension. Eur Respir J. 2019;54(6):1900378.
Article CAS PubMed PubMed Central Google Scholar
Wits M, Becher C, de Man F, Sanchez-Duffhues G, Goumans MJ. Sex-biased TGFβ signalling in pulmonary arterial hypertension. Cardiovasc Res. 2023;119(13):2262–77.
Article CAS PubMed PubMed Central Google Scholar
Qin S, Predescu DN, Patel M, et al. Sex differences in the proliferation of pulmonary artery endothelial cells: implications for plexiform arteriopathy. J Cell Sci. 2020;133(9):jcs237776.
Article CAS PubMed PubMed Central Google Scholar
Sangam S, Sun X, Schwantes-An TH, et al. SOX17 deficiency mediates pulmonary hypertension: At the crossroads of sex, metabolism, and genetics. Am J Respir Crit Care Med. 2023;207(8):1055–69.
Article CAS PubMed PubMed Central Google Scholar
Rigoulet M, Bouchez CL, Paumard P, Ransac S, Cuvellier S, Duvezin-Caubet S,...& Devin A (2020) Cell energy metabolism: An update. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1861(11), 148276.
Liu N, Parry S, Xiao Y, Zhou S, Liu Q. Molecular targets of the Warburg effect and inflammatory cytokines in the pathogenesis of pulmonary artery hypertension. Clin Chim Acta. 2017;466:98–104.
Article CAS PubMed Google Scholar
Peng H, Xiao Y, Deng X, Luo J, Hong C, Qin X. The Warburg effect: A new story in pulmonary arterial hypertension. Clin Chim Acta. 2016;461:53–8.
Article CAS PubMed Google Scholar
Dabral S, Muecke C, Valasarajan C, Schmoranzer M, Wietelmann A, Semenza G L,...& Pullamsetti SS (2019) A RASSF1A-HIF1α loop drives Warburg effect in cancer and pulmonary hypertension. Nat Commun, 10(1), 2130.
Zheng Q, Lu W, Yan H, et al. Established pulmonary hypertension in rats was reversed by a combination of a HIF-2α antagonist and a p53 agonist. Br J Pharmacol. 2022;179(5):1065–81.
Article CAS PubMed Google Scholar
Sun X, Sun BL, Babicheva A, et al. Direct extracellular NAMPT involvement in pulmonary hypertension and vascular remodeling Transcriptional regulation by SOX and HIF-2α. Am J Respir Cell Mol Biol. 2020;63(1):92–103.
Article CAS PubMed PubMed Central Google Scholar
Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y,...& Zhao Y (2019) Metabolic regulation of gene expression by histone lactylation. Nature, 574(7779), 575–580.
Cui H, Xie N, Banerjee S, Ge J, Jiang D, Dey T,...& Liu G (2021) Lung myofibroblasts promote macrophage profibrotic activity through lactate-induced histone lactylation. Am J Respir Cell Molecular Biol, 64(1), 115–125
Comments (0)