Activation of lung p53 by nutlin-3a prevents and reverses experimental pulmonary hypertension

Circulation

Volumn 127, Issue 16, 2013, Pages 1664-1676

  Mouraret, Nathalie ^a   Marcos, Elisabeth ^a   Abid, Shariq ^a   Gary Bobo, Guillaume ^a   Saker, Mirna ^a   Houssaini, Amal ^a   Dubois Rande, Jean Luc ^b   Boyer, Laurent ^a   Boczkowski, Jorge ^a   Derumeaux, Geneviève ^c   Amsellem, Valérie ^a   Adnot, Serge ^a  

^a INSERM U955   (France)

^b HENRI MONDOR HOSPITAL   (France)

^c UNIVERSITÉ DE LYON   (France)

Author keywords

cell aging; hypertension; muscles; pulmonary artery; ventricular remodeling

Indexed keywords

NUTLIN 3; PROTEIN; PROTEIN BAX; PROTEIN BTG2; PROTEIN MDM2; PROTEIN P21; PROTEIN P53; PUMA PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; HEART RIGHT VENTRICLE HYPERTROPHY; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PULMONARY ARTERY; PULMONARY ARTERY SMOOTH MUSCLE CELL; PULMONARY HYPERTENSION; SENESCENCE; SMOOTH MUSCLE FIBER; TRANSTHORACIC ECHOCARDIOGRAPHY;

ANIMALS; ANOXIA; APOPTOSIS; CELL AGING; CELLS, CULTURED; CYCLIN-DEPENDENT KINASE INHIBITOR P21; DRUG EVALUATION, PRECLINICAL; ENDOTHELIAL CELLS; GENE EXPRESSION REGULATION; GENES, P53; HUMANS; HYPERTENSION, PULMONARY; IMIDAZOLES; INDOLES; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; PHOSPHORYLATION; PIPERAZINES; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STABILITY; PULMONARY ARTERY; PYRROLES; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SINGLE-BLIND METHOD; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84876577725     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.113.002434     Document Type: Article

References (38)

1. Morrell NW, Adnot S, Archer SL, Dupuis J, Jones PL, MacLean MR, McMurtry IF, Stenmark KR, Thistlethwaite PA, Weissmann N, Yuan JX, Weir EK. Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S20-S31.
2. Eddahibi S, Humbert M, Fadel E, Raffestin B, Darmon M, Capron F, Simonneau G, Dartevelle P, Hamon M, Adnot S. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest. 2001;108:1141-1150.
3. Yeager ME, Halley GR, Golpon HA, Voelkel NF, Tuder RM. Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension. Circ Res. 2001;88:E2-E11.
4. Lee SD, Shroyer KR, Markham NE, Cool CD, Voelkel NF, Tuder RM. Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension. J Clin Invest. 1998;101:927-934.
5. Eddahibi S, Guignabert C, Barlier-Mur AM, Dewachter L, Fadel E, Dartevelle P, Humbert M, Simonneau G, Hanoun N, Saurini F, Hamon M, Adnot S. Cross talk between endothelial and smooth muscle cells in pulmonary hypertension: critical role for serotonin-induced smooth muscle hyperplasia. Circulation. 2006;113:1857-1864.
6. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation. 2002;105:1672-1678.
7. McMurtry MS, Archer SL, Altieri DC, Bonnet S, Haromy A, Harry G, Bonnet S, Puttagunta L, Michelakis ED. Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest. 2005;115:1479-1491.
8. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005;115:2811-2821.
9. Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007;26:2157-2165.
10. Kubbutat MH, Jones SN, Vousden KH. Regulation of p53 stability by Mdm2. Nature. 1997;387:299-303.
11. Mayo LD, Donner DB. The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network. Trends Biochem Sci. 2002;27:462-467.
12. Vargas DA, Takahashi S, Ronai Z. Mdm2: A regulator of cell growth and death. Adv Cancer Res. 2003;89:1-34.
13. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004;303:844-848.
14. Vousden KH. Outcomes of p53 activation-spoilt for choice. J Cell Sci. 2006;119(Pt 24):5015-5020.
15. Alimonti A, Nardella C, Chen Z, Clohessy JG, Carracedo A, Trotman LC, Cheng K, Varmeh S, Kozma SC, Thomas G, Rosivatz E, Woscholski R, Cognetti F, Scher HI, Pandolf PP. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J Clin Invest. 2010;120:681-693.
16. Hashimoto T, Ichiki T, Ikeda J, Narabayashi E, Matsuura H, Miyazaki R, Inanaga K, Takeda K, Sunagawa K. Inhibition of MDM2 attenuates neointimal hyperplasia via suppression of vascular proliferation and in-fammation. Cardiovasc Res. 2011;91:711-719.
17. Ihling C, Haendeler J, Menzel G, Hess RD, Fraedrich G, Schaefer HE, Zeiher AM. Co-expression of p53 and MDM2 in human atherosclerosis: implications for the regulation of cellularity of atherosclerotic lesions. J Pathol. 1998;185:303-312.
18. Nakamura Y, Suzuki S, Suzuki T, Ono K, Miura I, Satoh F, Moriya T, Saito H, Yamada S, Ito S, Sasano H. MDM2: a novel mineralocorticoid-responsive gene involved in aldosterone-induced human vascular structural remodeling. Am J Pathol. 2006;169:362-371.
19. An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM. Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature. 1998;392:405-408.
20. Efeyan A, Ortega-Molina A, Velasco-Miguel S, Herranz D, Vassilev LT, Serrano M. Induction of p53-dependent senescence by the MDM2 antagonist nutlin-3a in mouse cells of fbroblast origin. Cancer Res. 2007;67:7350-7357.
21. Kumamoto K, Spillare EA, Fujita K, Horikawa I, Yamashita T, Appella E, Nagashima M, Takenoshita S, Yokota J, Harris CC. Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res. 2008;68:3193-3203.
22. Huang B, Deo D, Xia M, Vassilev LT. Pharmacologic p53 activation blocks cell cycle progression but fails to induce senescence in epithelial cancer cells. Mol Cancer Res. 2009;7:1497-1509.
23. Miyachi M, Kakazu N, Yagyu S, Katsumi Y, Tsubai-Shimizu S, Kikuchi K, Tsuchiya K, Iehara T, Hosoi H. Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cells. Clin Cancer Res. 2009;15:4077-4084.
24. Noureddine H, Gary-Bobo G, Alifano M, Marcos E, Saker M, Vienney N, Amsellem V, Maitre B, Chaouat A, Chouaid C, Dubois-Rande JL, Damotte D, Adnot S. Pulmonary artery smooth muscle cell senescence is a pathogenic mechanism for pulmonary hypertension in chronic lung disease. Circ Res. 2011;109:543-553.
25. Ciuclan L, Bonneau O, Hussey M, Duggan N, Holmes AM, Good R, Stringer R, Jones P, Morrell NW, Jarai G, Walker C, Westwick J, Thomas M. A novel murine model of severe pulmonary arterial hypertension. Am J Respir Crit Care Med. 2011;184:1171-1182.
26. Guignabert C, Izikki M, Tu LI, Li Z, Zadigue P, Barlier-Mur AM, Hanoun N, Rodman D, Hamon M, Adnot S, Eddahibi S. Transgenic mice over-expressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res. 2006;98:1323-1330.
27. Gary-Bobo G, Houssaini A, Amsellem V, Rideau D, Pacaud P, Perrin A, Brégeon J, Marcos E, Dubois-Randé JL, Sitbon O, Savale L, Adnot S. Effects of HIV protease inhibitors on progression of monocro-taline-and hypoxia-induced pulmonary hypertension in rats. Circulation. 2010;122:1937-1947.
28. Mizuno S, Bogaard HJ, Kraskauskas D, Alhussaini A, Gomez-Arroyo J, Voelkel NF, Ishizaki T. p53 Gene defciency promotes hypoxia-induced pulmonary hypertension and vascular remodeling in mice. Am J Physiol Lung Cell Mol Physiol. 2011;300:L753-L761.
29. Nardella C, Clohessy JG, Alimonti A, Pandolf PP. Pro-senescence therapy for cancer treatment. Nat Rev Cancer. 2011;11:503-511.
30. Wade M, Wang YV, Wahl GM. The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol. 2010;20:299-309.
31. Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, Nikolovska-Coleska Z, Ding K, Wang G, Chen J, Bernard D, Zhang J, Lu Y, Gu Q, Shah RB, Pienta KJ, Ling X, Kang S, Guo M, Sun Y, Yang D, Wang S. Temporal activation of p53 by a specifc MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc Natl Acad Sci USA. 2008;105:3933-3938.
32. Lane DP, Brown CJ, Verma C, Cheok CF. New insights into p53 based therapy. Discov Med. 2011;12:107-117.
33. Sano M, Minamino T, Toko H, Miyauchi H, Orimo M, Qin Y, Akazawa H, Tateno K, Kayama Y, Harada M, Shimizu I, Asahara T, Hamada H, Tomita S, Molkentin JD, Zou Y, Komuro I. p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature. 2007;446:444-448.
34. Wei Q, Dong G, Yang T, Megyesi J, Price PM, Dong Z. Activation and involvement of p53 in cisplatin-induced nephrotoxicity. Am J Physiol Renal Physiol. 2007;293:F1282-F1291.
35. Meek DW, Knippschild U. Posttranslational modifcation of MDM2. Mol Cancer Res. 2003;1:1017-1026.
36. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120:513-522.
37. Amsellem V, Gary-Bobo G, Marcos E, Maitre B, Chaar V, Validire P, Stern JB, Noureddine H, Sapin E, Rideau D, Hue S, Le Corvoisier P, Le Gouvello S, Dubois-Randé JL, Boczkowski J, Adnot S. Telomere dysfunction causes sustained infammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;184:1358-1366.
38. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479:232-236.