The PPARα/p16INK4a pathway inhibits vascular smooth muscle cell proliferation by repressing cell cycle-dependent telomerase activation

Circulation Research

Volumn 103, Issue 10, 2008, Pages 1155-1163

  Gizard, Florence ^a   Nomiyama, Takashi ^a   Zhao, Yue ^a   Findeisen, Hannes M ^a   Heywood, Elizabeth B ^a   Jones, Karrie L ^a   Staels, Bart ^b,c,d,e   Bruemmer, Dennis ^a,f  

^a U545   (France)

^b INSTITUT PASTEUR DE LILLE   (France)

^c U545   (France)

^d INSERM   (France)

^e UNIV LILLE   (France)

^f UNIVERSITY OF KENTUCKY   (United States)

Author keywords

P16ink4a; PPAR a; Smooth muscle cells; Telomerase; Transcriptional regulation

Indexed keywords

2 [4 [2 [3 CYCLOHEXYL 1 (4 CYCLOHEXYLBUTYL)UREIDO]ETHYL]PHENYLTHIO] 2 METHYLPROPIONIC ACID; CYCLIN DEPENDENT KINASE INHIBITOR 2A; FENOFIBRIC ACID; GEMFIBROZIL; MITOGENIC AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PIRINIXIC ACID; PROTEIN P107; PROTEIN P130; PROTEIN P16; TELOMERASE REVERSE TRANSCRIPTASE; TRANSCRIPTION FACTOR E2F1; E2F1 PROTEIN, MOUSE; E2F1 PROTEIN, RAT; RBL1 PROTEIN, MOUSE; RBL2 PROTEIN, MOUSE; RBL2 PROTEIN, RAT; TELOMERASE; TERT PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD VESSEL INJURY; CELL CYCLE; CELL FUNCTION; CELL PROLIFERATION; CONTROLLED STUDY; DRUG EFFECT; DRUG INHIBITION; ENZYME ACTIVATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; PROTEIN EXPRESSION; RAT; SMOOTH MUSCLE FIBER; VASCULAR SMOOTH MUSCLE; ANIMAL; BIOSYNTHESIS; CELL CULTURE; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; DRUG POTENTIATION; DYSLIPIDEMIA; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; PHYSIOLOGY;

ANIMALS; CELLS, CULTURED; CYCLIN-DEPENDENT KINASE INHIBITOR P16; DYSLIPIDEMIAS; E2F1 TRANSCRIPTION FACTOR; ENZYME ACTIVATION; G1 PHASE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; MICE; MITOGENS; MYOCYTES, SMOOTH MUSCLE; PPAR ALPHA; PROMOTER REGIONS, GENETIC; RATS; RETINOBLASTOMA-LIKE PROTEIN P107; RETINOBLASTOMA-LIKE PROTEIN P130; S PHASE; TELOMERASE; TRANSCRIPTION, GENETIC;

EID: 63849146427     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.108.186205     Document Type: Article

References (33)

1. Dzau VJ, Braun-Dullaeus RC, Sedding DG. Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med. 2002;8:1249-1256.
2. Harbour JW, Dean DC. Rb function in cell-cycle regulation and apopto-sis. Nat Cell Biol. 2000;2:E65-E67.
3. Sherr CJ, Roberts JM. Living with or without cyclins and cyclin-dependent kinases. Genes Dev. 2004;18:2699-2711.
4. 4. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet. 2005;6:611-622. (Pubitemid 41044298)
5. Chan SW, Blackburn EH. New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin. Oncogene. 2002;21: 553-563.
6. 6. Poole JC, Andrews LG, Tollefsbol TO. Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene. 2001; 269:1-12. (Pubitemid 32488901)
7. Cao Y, Li H, Mu FT, Ebisui O, Funder JW, Liu JP. Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. FASEB J. 2002;16:96-98.
8. 8. Minamino T, Kourembanas S. Mechanisms of telomerase induction during vascular smooth muscle cell proliferation. Circ Res. 2001;89: 237-243. (Pubitemid 34132681)
9. 9. Ogawa D, Nomiyama T, Nakamachi T, Heywood EB, Stone JF, Berger JP, Law RE, Bruemmer D. Activation of peroxisome proliferator-acti-vated receptor gamma suppresses telomerase activity in vascular smooth muscle cells. Circ Res. 2006;98:e50-e59. (Pubitemid 43755233)
10. 10. Minamino T, Komuro I. The role of telomerase activation in the regu-lation of vascular smooth muscle cell proliferation. Drug News Perspect. 2003;16:211-216. (Pubitemid 37039402)
11. Fuster JJ, Andres V. Telomere biology and cardiovascular disease. Circ Res. 2006;99:1167-1180.
12. 12. Lefebvre P, Chinetti G, Fruchart JC, Staels B. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest. 2006;116:571-580. (Pubitemid 43326861)
13. 13. Glass CK. Going nuclear in metabolic and cardiovascular disease. J Clin Invest. 2006;116:556-560. (Pubitemid 43326859)
14. 14. Gizard F, Amant C, Barbier O, Bellosta S, Robillard R, Percevault F, Sevestre H, Krimpenfort P, Corsini A, Rochette J, Glineur C, Fruchart JC, Torpier G, Staels B. PPAR alpha inhibits vascular smooth muscle cell proliferation underlying intimai hyperplasia by inducing the tumor sup-pressor p16INK4a. J Clin Invest. 2005;115:3228-3238. (Pubitemid 41567587)
15. Brown PJ, Stuart LW, Hurley KP, Lewis MC, Winegar DA, Wilson JG, Wilkison WO, Ittoop OR, Willson TM. Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis. Bioorg Med Chem Lett. 2001;11:1225-1227.
16. 16. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43:527-550. (Pubitemid 30127149)
17. 17. Crowe DL, Nguyen DC, Tsang KJ, Kyo S. E2F-1 represses transcription of the human telomerase reverse transcriptase gene. Nucleic Acids Res. 2001;29:2789-2794. (Pubitemid 32685042)
18. Won J, Yim J, Kim TK. Opposing regulatory roles of E2F in human telomerase reverse transcriptase (hTERT) gene expression in human tumor and normal somatic cells. FASEB J. 2002;16:1943-1945.
19. 19. Duez H, Lefebvre B, Poulain P, Torra IP, Percevault F, Luc G, Peters JM, Gonzalez FJ, Gineste R, Helleboid S, Dzavik V, Fruchart JC, Fievet C, Lefebvre P, Staels B. Regulation of human apoA-I by gemfibrozil and fenofibrate through selective peroxisome proliferator-activated receptor alpha modulation. Arterioscler Thromb Vase Biol. 2005;25:585-591. (Pubitemid 40315682)
20. 20. Torella D, Leosco D, Indolfi C, Curcio A, Coppola C, Ellison GM, Russo VG, Torella M, Volti GL, Rengo F, Chiariello M. Aging exacerbates negative remodeling and impairs endothelial regeneration after balloon injury. Am J Physiol Heart Circ Physiol. 2004;287:H2850-H2860. (Pubitemid 39557160)
21. 21. Rayman JB, Takahashi Y, Indjeian VB, Dannenberg JH, Catchpole S, Watson RJ, te Riele H, Dynlacht BD. E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex. Genes Dev. 2002;16:933-947. (Pubitemid 34408543)
22. 22. Zhang HS, Postigo AA, Dean DC. Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition. Cell. 1999;97:53-61. (Pubitemid 129746808)
23. Bruce JL, Hurford RK Jr, Classon M, Koh J, Dyson N. Requirements for cell cycle arrest by p16INK4a. Mol Cell. 2000;6:737-742.
24. Claudio PP, Fratta L, Farina F, Howard CM, Stassi G, Numata S, Pacilio C, Davis A, Lavitrano M, Volpe M, Wilson JM, Trimarco B, Giordano A, Condorelli G. Adenoviral RB2/p130 gene transfer inhibits smooth muscle cell proliferation and prevents restenosis after angioplasty. Circ Res. 1999;85:1032-1039.
25. 25. Sindermann JR, Smith J, Kobbert C, Plenz G, Skaletz-Rorowski A, Solomon JL, Fan L, March KL. Direct evidence for the importance of p130 in injury response and arterial remodeling following carotid artery ligation. Cardiovasc Res. 2002;54:676-683. (Pubitemid 34595427)
26. McMurtry MS, Archer SL, Altieri DC, Bonnet S, Haromy A, Harry G, 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.
27. Conte MS, Altieri DC. Survivin regulation of vascular injury. Trends Cardiovasc Med. 2006;16:114-117.
28. 28. van der Veer E, Nong Z, O'Neil C, Urquhart B, Freeman D, Pickering JG. Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell matu-ration. Circ Res. 2005;97:25-34. (Pubitemid 40982319)
29. 29. Endoh T, Tsuji N, Asanuma K, Yagihashi A, Watanabe N. Survivin enhances telomerase activity via up-regulation of specificity protein 1-and c-Myc-mediated human telomerase reverse transcriptase gene tran-scription. Exp Cell Res. 2005;305:300-311. (Pubitemid 40462542)
30. 30. Jiang Y, Saavedra HI, Holloway MP, Leone G, Altura RA. Aberrant regulation of survivin by the RB/E2F family of proteins. J Biol Chem. 2004;279:40511-40520. (Pubitemid 39287642)
31. 31. van der Veer E, Ho C, O'Neil C, Barbosa N, Scott R, Cregan SP, Pickering JG. Extension of human cell lifespan by nicotinamide phos-phoribosyltransferase. J Biol Chem. 2007;282:10841-10845. (Pubitemid 47100731)
32. 32. Laufs U, Marra D, Node K, Liao JK. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing Rho GTPase-induced down-regulation of p27Kipl. J Biol Chem. 1999;274:21926-21931. (Pubitemid 129519746)
33. 33. Paumelle R, Blanquart C, Briand O, Barbier O, Duhem C, Woerly G, Percevault F, Fruchart JC, Dombrowicz D, Glineur C, Staels B. Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway. Circ Res. 2006;98:361-369. (Pubitemid 43755332)