Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension

Journal of Clinical Investigation

Volumn 126, Issue 9, 2016, Pages 3207-3218

  Guignabert, Christophe ^a,b,c   Phan, Carole ^a,b,c   Seferian, Andrei ^a,b,c   Huertas, Alice ^a,b,c   Tu, Ly ^a,b,c   Thuillet, Raphaël ^a,b,c   Sattler, Caroline ^a,b,c   Hiress, Morane Le ^a,b,c   Tamura, Yuichi ^a,b,c   Jutant, Etienne Marie ^a,b,c   Chaumais, Marie Camille ^a,b,c   Bouchet, Stéphane ^d,e   Manéglier, Benjamin ^f   Molimard, Mathieu ^d,e   Rousselot, Philippe ^f,g   Sitbon, Olivier ^a,b,c   Simonneau, Gérald ^a,b,c   Montani, David ^a,b,c   Humbert, Marc ^a,b,c  

^a Universite Paris Sud   (France)

^b UNIVERSITÉ PARIS SACLAY   (France)

^c BICÊTRE HOSPITAL   (France)

^d BORDEAUX UNIVERSITY HOSPITAL   (France)

^e UNIVERSITÉ DE BORDEAUX   (France)

^f CENTRE HOSPITALIER DE VERSAILLES   (France)

^g LABORATOIRE DES SCIENCES DU CLIMAT ET DE L ENVIRONNEMENT   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 6; ANGIOPOIETIN RECEPTOR; CASPASE 3; CASPASE 7; CATALASE; COPPER ZINC SUPEROXIDE DISMUTASE; DASATINIB; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; FLAVIN CONTAINING MONOOXYGENASE 2; GA BINDING PROTEIN; GLUCOSE REGULATED PROTEIN 78; GLUTATHIONE PEROXIDASE; HEME OXYGENASE 1; IMATINIB; INDUCIBLE NITRIC OXIDE SYNTHASE; INITIATION FACTOR 2ALPHA; INOSITOL REQUIRING ENZYME 1ALPHA; INTERCELLULAR ADHESION MOLECULE 1; PROTEIN; PROTEIN TYROSINE KINASE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1; X BOX BINDING PROTEIN 1; ANTINEOPLASTIC AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CD3+ T LYMPHOCYTE; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL (TOPIC); CONTROLLED STUDY; DISEASE PREDISPOSITION; ENDOTHELIAL DYSFUNCTION; EXPERIMENTAL PULMONARY HYPERTENSION; HUMAN; HYPOXIC LUNG VASOCONSTRICTION; LUNG ENDOTHELIUM; LUNG TOXICITY; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PULMONARY HYPERTENSION; RAT; SIDE EFFECT; VASCULAR REMODELING; ADULT; ANIMAL; BLOOD; CELL CULTURE; CHEMICALLY INDUCED; DRUG EFFECTS; FEMALE; GENETIC PREDISPOSITION; HEMODYNAMICS; HYPOXIA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; LUNG; METABOLISM; MIDDLE AGED; MITOCHONDRION; PATHOLOGY; RANDOMIZED CONTROLLED TRIAL; VASCULARIZATION;

ADULT; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELLS, CULTURED; DASATINIB; E-SELECTIN; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HEMODYNAMICS; HUMANS; HYPERTENSION, PULMONARY; HYPOXIA; IMATINIB MESYLATE; INTERCELLULAR ADHESION MOLECULE-1; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; LUNG; MALE; MIDDLE AGED; MITOCHONDRIA; RATS; REACTIVE OXYGEN SPECIES; VASCULAR CELL ADHESION MOLECULE-1;

EID: 84987786680     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI86249     Document Type: Article

References (45)

1. Galiè N, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46(4):903-975
2. Guignabert C, Dorfmuller P. Pathology and pathobiology of pulmonary hypertension. Semin Respir Crit Care Med. 2013;34(5):551-559
3. Guignabert C, et al. New molecular targets of pulmonary vascular remodeling in pulmonary arterial hypertension: importance of endothelial communication. Chest. 2015;147(2):529-537
4. Guignabert C, et al. Pathogenesis of pulmonary arterial hypertension: lessons from cancer. Eur Respir Rev. 2013;22(130):543-551
5. Huertas A, et al. Immune dysregulation and endothelial dysfunction in pulmonary arterial hypertension: a complex interplay. Circulation. 2014;129(12):1332-1340
6. Rabinovitch M, Guignabert C, Humbert M, Nicolls MR. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension. Circ Res. 2014;115(1):165-175
7. Tuder RM, et al. Relevant issues in the pathology and pathobiology of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 suppl):D4-D12
8. Simonneau G, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 suppl):D34-D41
9. Montani D, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;125(17):2128-2137
10. Bantscheff M, et al. Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol. 2007;25(9):1035-1044
11. Shaker ME, Zalata KR, Mehal WZ, Shiha GE, Ibrahim TM. Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis. Toxicol Appl Pharmacol. 2011;252(2):165-175
12. Kim Y, et al. Anti-fibrotic activity and enhanced interleukin-6 production by hepatic stellate cells in response to imatinib mesylate. Liver Int. 2012;32(6):1008-1017
13. Sommer N, Strielkov I, Pak O, Weissmann N. Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction. Eur Respir J. 2016;47(1):288-303
14. Witte I, Horke S. Assessment of endoplasmic reticulum stress and the unfolded protein response in endothelial cells. Meth Enzymol. 2011;489:127-146
15. McAlpine CS, Werstuck GH. The development and progression of atherosclerosis: evidence supporting a role for endoplasmic reticulum (ER) stress signaling. Cardiovasc Hematol Disord Drug Targets. 2013;13(2):158-164
16. Lenna S, Han R, Trojanowska M. Endoplasmic reticulum stress and endothelial dysfunction. IUBMB Life. 2014;66(8):530-537
17. Dromparis P, Paulin R, Sutendra G, Qi AC, Bonnet S, Michelakis ED. Uncoupling protein 2 deficiency mimics the effects of hypoxia and endoplasmic reticulum stress on mitochondria and triggers pseudohypoxic pulmonary vascular remodeling and pulmonary hypertension. Circ Res. 2013;113(2):126-136
18. Dromparis P, Paulin R, Stenson TH, Haromy A, Sutendra G, Michelakis ED. Attenuating endoplasmic reticulum stress as a novel therapeutic strategy in pulmonary hypertension. Circulation. 2013;127(1):115-125
19. Huertas A, et al. Leptin signalling system as a target for pulmonary arterial hypertension therapy. Eur Respir J. 2015;45(4):1066-1080
20. Ricard N, et al. Increased pericyte coverage mediated by endothelial-derived fibroblast growth factor-2 and interleukin-6 is a source of smooth muscle-like cells in pulmonary hypertension. Circulation. 2014;129(15):1586-1597
21. de Man FS, et al. Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012;186(8):780-789
22. Tu L, et al. A critical role for p130Cas in the progression of pulmonary hypertension in humans and rodents. Am J Respir Crit Care Med. 2012;186(7):666-676
23. Tu L, et al. Autocrine fibroblast growth factor-2 signaling contributes to altered endothelial phenotype in pulmonary hypertension. Am J Respir Cell Mol Biol. 2011;45(2):311-322
24. Eddahibi S, et al. Cross talk between endothelial and smooth muscle cells in pulmonary hypertension: critical role for serotonin-induced smooth muscle hyperplasia. Circulation. 2006;113(15):1857-1864
25. Wang GF, et al. Geniposide inhibits high glucose-induced cell adhesion through the NF-kappaB signaling pathway in human umbilical vein endothelial cells. Acta Pharmacol Sin. 2010;31(8):953-962
26. Lutters BC, Leeuwenburgh MA, Appeldoorn CC, Molenaar TJ, Van Berkel TJ, Biessen EA. Blocking endothelial adhesion molecules: a potential therapeutic strategy to combat atherogenesis. Curr Opin Lipidol. 2004;15(5):545-552
27. Xue T, et al. Oxidative stress is involved in Dasatinib-induced apoptosis in rat primary hepatocytes. Toxicol Appl Pharmacol. 2012;261(3):280-291
28. Pullamsetti SS, et al. Role of Src tyrosine kinases in experimental pulmonary hypertension. Arterioscler Thromb Vasc Biol. 2012;32(6):1354-1365
29. Goldthorpe H, et al. Occlusive lung arterial lesions in endothelial-targeted, fas-induced apoptosis transgenic mice. Am J Respir Cell Mol Biol. 2015;53(5):712-718
30. Guignabert C, et al. Tie2-mediated loss of peroxisome proliferator-activated receptor-gamma in mice causes PDGF receptor-beta-dependent pulmonary arterial muscularization. Am J Physiol Lung Cell Mol Physiol. 2009;297(6):L1082-L1090
31. Long L, et al. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nat Med. 2015;21(7):777-785
32. Schermuly RT, et al. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005;115(10):2811-2821
33. Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer. 2007;7(5):345-356
34. Kamath AV, Wang J, Lee FY, Marathe PH. Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL. Cancer Chemother Pharmacol. 2008;61(3):365-376
35. Korashy HM, Rahman AF, Kassem MG. Dasatinib. Profiles Drug Subst Excip Relat Methodol. 2014;39:205-237
36. Druker BJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031-1037
37. Nagaraj C, et al. Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries. Eur Respir J. 2013;41(1):85-95
38. El Hachmane MF, Rees KA, Veale EL, Sumbayev VV, Mathie A. Enhancement of TWIK-related acid-sensitive potassium channel 3 (TASK3) two-pore domain potassium channel activity by tumor necrosis factor and alpha. J Biol Chem. 2014;289(3):1388-1401
39. Lauritzen I, et al. K+-dependent cerebellar granule neuron apoptosis. Role of task leak K+ channels. J Biol Chem. 2003;278(34):32068-32076
40. Trimarchi JR, Liu L, Smith PJ, Keefe DL. Apoptosis recruits two-pore domain potassium channels used for homeostatic volume regulation. Am J Physiol Cell Physiol. 2002;282(3):C588-C594
41. Cain K, Langlais C, Sun XM, Brown DG, Cohen GM. Physiological concentrations of K+ inhibit cytochrome c-dependent formation of the apoptosome. J Biol Chem. 2001;276(45):41985-41990
42. Hughes FM, Bortner CD, Purdy GD, Cidlowski JA. Intracellular K+ suppresses the activation of apoptosis in lymphocytes. J Biol Chem. 1997;272(48):30567-30576
43. Bouchet S, et al. Simultaneous determination of nine tyrosine kinase inhibitors by 96-well solid-phase extraction and ultra performance LC/MS-MS. Clin Chim Acta. 2011;412(11-12):1060-1067
44. Guignabert C, et al. Dichloroacetate treatment partially regresses established pulmonary hypertension in mice with SM22α-targeted overexpression of the serotonin transporter. FASEB J. 2009;23(12):4135-4147
45. Le Hiress M, et al. Proinflammatory signature of the dysfunctional endothelium in pulmonary hypertension. Role of the macrophage migration inhibitory factor/CD74 complex. Am J Respir Crit Care Med. 2015;192(8):983-997