Indirubin-3′-monoxime blocks vascular smooth muscle cell proliferation by inhibition of signal transducer and activator of transcription 3 signaling and reduces neointima formation in vivo

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 30, Issue 12, 2010, Pages 2475-2481

  Schwaiberger, Andrea V ^a   Heiss, Elke H ^a   Cabaravdic, Muris ^b   Oberan, Tina ^a   Zaujec, Jan ^b   Schachner, Daniel ^a   Uhrin, Pavel ^b   Atanasov, Atanas G ^a   Breuss, Johannes M ^b   Binder, Bernd R ^b   Dirsch, Verena M ^a  

^a UNIVERSITY OF VIENNA   (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

indirubin; neointima; proliferation; STAT3; vascular smooth muscle cell

Indexed keywords

ARGININE; BROXURIDINE; CITRULLINE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GAMMA INTERFERON; INDIRUBIN; INDIRUBIN 3' MONOXIME; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PLATELET DERIVED GROWTH FACTOR; PROTEIN KINASE B; STAT3 PROTEIN; SYNAPTOPHYSIN; THROMBIN; UNCLASSIFIED DRUG; INDIRUBIN-3'-MONOXIME; INDOLE DERIVATIVE; KI 67 ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE; OXIME; PLATELET DERIVED GROWTH FACTOR BB; PLATELET-DERIVED GROWTH FACTOR BB; STAT3 PROTEIN, MOUSE; STAT3 PROTEIN, RAT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL CYCLE ARREST; CELL PROLIFERATION; CONTROLLED STUDY; DOSE RESPONSE; EMBRYO; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; MOUSE; NEOINTIMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RAT; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; VASCULAR SMOOTH MUSCLE; ANIMAL; C57BL MOUSE; CELL CULTURE; CELL CYCLE; DISEASE MODEL; DRUG ANTAGONISM; DRUG EFFECT; ENDOTHELIUM CELL; FEMORAL ARTERY; FLOW CYTOMETRY; GENETIC TRANSFECTION; GENETICS; HYPERPLASIA; METABOLISM; PATHOLOGY; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PHOSPHORYLATION; SPRAGUE DAWLEY RAT; STENOSIS, OCCLUSION AND OBSTRUCTION; TIME;

ANIMALS; ARTERIAL OCCLUSIVE DISEASES; CELL CYCLE; CELL PROLIFERATION; CELLS, CULTURED; CONSTRICTION, PATHOLOGIC; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOTHELIAL CELLS; FEMORAL ARTERY; FLOW CYTOMETRY; HUMANS; HYPERPLASIA; INDOLES; INTERFERON-GAMMA; KI-67 ANTIGEN; MALE; MICE; MICE, INBRED C57BL; MITOGEN-ACTIVATED PROTEIN KINASES; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; OXIMES; PHOSPHORYLATION; PLATELET-DERIVED GROWTH FACTOR; PROTO-ONCOGENE PROTEINS C-AKT; RATS; RATS, SPRAGUE-DAWLEY; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; THROMBIN; TIME FACTORS; TRANSFECTION;

EID: 78650416450     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.110.212654     Document Type: Article

References (45)

1. Breuss JM, Cejna M, Bergmeister H, Kadl A, Baumgartl G, Steurer S, Xu Z, Koshelnick Y, Lipp J, De Martin R, Losert U, Lammer J, Binder BR. Activation of nuclear factor- KB significantly contributes to lumen loss in a rabbit iliac artery balloon angioplasty model. Circulation. 2002;105: 633-638.
2. Dzau VJ, Braun-Dullaeus RC, Sedding DG. Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med. 2002;8:1249-1256.
3. Costa MA, Simon DI. Molecular basis of restenosis and drugeluting stents. Circulation. 2005;111:2257-2273.
4. Maisel WH. Unanswered questions: drugeluting stents and the risk of late thrombosis. N Engl J Med. 2007;356:981-984.
5. Wessely R, Schomig A, Kastrati A. Sirolimus and Paclitaxel on polymer-based drugeluting stents: similar but different. J Am Coll Cardiol. 2006;47:708-714. (Pubitemid 43243089)
6. Hoessel R, Leclerc S, Endicott JA, Nobel ME, Lawrie A, Tunnah P, Leost M, Damiens E, Marie D, Marko D, Niederberger E, Tang W, Eisenbrand G, Meijer L. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat Cell Biol. 1999;1: 60-67.
7. Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R, Crovace C, Tarricone C, Musacchio A, Roe SM, Pearl L, Greengard P. GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol. 2003;10:1255-1266.
8. Polychronopoulos P, Magiatis P, Skaltsounis AL, Myrianthopoulos V, Mikros E, Tarricone A, Musacchio A, Roe SM, Pearl L, Leost M, Greengard P, Meijer L. Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem. 2004;47:935-946.
9. Ferandin Y, Bettayeb K, Kritsanida M, Lozach O, Polychronopoulos P, Magiatis P, Skaltsounis AL, Meijer L. 3'-Substituted 7-halogenoindirubins, a new class of cell death inducing agents. J Med Chem. 2006;49:4638-4649.
10. Damiens E, Baratte B, Marie D, Eisenbrand G, Meijer L. Anti-mitotic properties of indirubin-3'-monoxime, a CDK/GSK-3 inhibitor: induction of endoreplication following prophase arrest. Oncogene. 2001;20: 3786-3797.
11. Knockaert M, Blondel M, Bach S, Leost M, Elbi C, Hager GL, Nagy SR, Han D, Denison M, Ffrench M, Ryan XP, Magiatis P, Polychronopoulos P, Greengard P, Skaltsounis L, Meijer L. Independent actions on cyclin-dependent kinases and aryl hydrocarbon receptor mediate the antiproliferative effects of indirubins. Oncogene. 2004;23:4400-4412.
12. Nam S, Buettner R, Turkson J, Kim D, Cheng JQ, Muehlbeyer S, Hippe F, Vatter S, Merz KH, Eisenbrand G, Jove R. Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells. Proc Natl Acad Sci USA. 2005;102:5998-6003.
13. Ribas J, Bettayeb K, Ferandin Y, Knockaert M, Garrofe-Ochoa X, Totzke F, Schachtele C, Mester J, Polychronopoulos P, Magiatis P, Skaltsounis AL, Boix J, Meijer L. 7-Bromoindirubin-3'-oxime induces caspase-independent cell death. Oncogene. 2006;25:6304-6318.
14. Sethi G, Ahn KS, Sandur SK, Lin X, Chaturvedi MM, Aggarwal BB. Indirubin enhances tumor necrosis factor-induced apoptosis through modulation of nuclear factor-kappa B signaling pathway. J Biol Chem. 2006; 281:23425-23435.
15. Haider UG, Roos TU, Kontaridis MI, Neel BG, Sorescu D, Griendling KK, Vollmar AM, Dirsch VM. Resveratrol inhibits angiotensin II- and epidermal growth factor-mediated Akt activation: role of Gab1 and Shp2. Mol Pharmacol. 2005;68:41-48.
16. Leikert JF, Rathel TR, Wohlfart P, Cheynier V, Vollmar AM, Dirsch VM. Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells. Circulation. 2002;106:1614-1617.
17. Haider UG, Sorescu D, Griendling KK, Vollmar AM, Dirsch VM. Resveratrol increases serine15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Mol Pharmacol. 2003;63:925-932.
18. Moroi M, Zhang L, Yasuda T, Virmani R, Gold HK, Fishman MC, Huang PL. Interaction of genetic deficiency of endothelial nitric oxide, gender, and pregnancy in vascular response to injury in mice. J Clin Invest. 1998;101:1225-1232.
19. Horvath CM, Wen Z, Darnell JE. A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain. Genes Dev. 1995;9:984-994.
20. Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE. Stat3 as an oncogene. Cell. 1999;98:295-303.
21. Sherr CJ. Cancer cell cycles. Science. 1996;274:1672-1677.
22. Napoli C, Ignarro LJ. Nitric oxide and atherosclerosis. Nitric Oxide. 2001;5:88-97.
23. Cooney R, Hynes SO, Sharif F, Howard L, O'Brien T. Effect of gene delivery of NOS isoforms on intimal hyperplasia and endothelial regeneration after balloon injury. Gene Ther. 2007;14:396-404.
24. Cooney R, Hynes SO, Duffy AM, Sharif F, O'Brien T. Adenoviral-mediated gene transfer of nitric oxide synthase isoforms and vascular cell proliferation. J Vasc Res. 2006;43:462-472.
25. Tsukada S, Iwai M, Nishiu J, Itoh M, Tomoike H, Horiuchi M, Nakamura Y, Tanaka T. Inhibition of experimental intimal thickening in mice lacking a novel G-protein-coupled receptor. Circulation. 2003;107: 313-319.
26. Engelse MA, Arkenbout EK, Pannekoek H, de Vries CJ. Activin and TR3 orphan receptor: two 'atheroprotective' genes as evidenced in dedicated mouse models. Clin Exp Pharmacol Physiol. 2003;30:894-899.
27. Berk BC. Vascular smooth muscle growth: autocrine growth mechanisms. Physiol Rev. 2001;81:999-1030.
28. Bowman T, Broome MA, Sinibaldi D, Wharton W, Pledger WJ, Sedivy JM, Irby R, Yeatman T, Courtneidge SA, Jove R. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mito-genesis. Proc Natl Acad Sci USA. 2001;98:7319-7324.
29. Simon AR, Takahashi S, Severgnini M, Fanburg BL, Cochran BH. Role of the JAK-STAT pathway in PDGF-stimulated proliferation of human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2002;282:L1296-L1304.
30. Tellides G, Tereb DA, Kirkiles-Smith NC, Kim RW, Wilson JH, Schechner JS, Lorber MI, Pober JS. Interferon-*/ elicits arteriosclerosis in the absence of leukocytes. Nature. 2000;403:207-211. (Pubitemid 30050965)
31. Harvey EJ, Ramji DP. Interferon-y and atherosclerosis: pro- or antiatherogenic? Cardiovasc Res. 2005;67:11-20.
32. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD. How cells respond to interferons. Annu Rev Biochem. 1998;67:227-264.
33. Madamanchi NR, Li S, Patterson C, Runge MS. Thrombin regulates vascular smooth muscle cell growth and heat shock proteins via the JAK-STAT pathway. J Biol Chem. 2001;276:18915-18924.
34. Schust J, Sperl B, Hollis A, Mayer TU, Berg T. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem Biol. 2006;13: 1235-1242.
35. Shibata R, Kai H, Seki Y, Kato S, Wada Y, Hanakawa Y, Hashimoto K, Yoshimura A, Imaizumi T. Inhibition of STAT3 prevents neointima formation by inhibiting proliferation and promoting apoptosis of neoin-timal smooth muscle cells. Hum Gene Ther. 2003;14:601-610.
36. Yu H, Jove R. The STATs of cancer: new molecular targets come of age. Nature Rev. 2004;4:97-105.
37. Seki Y, Kai H, Shibata R, Nagata T, Yasukawa H, Yoshimura A, Imaizumi T. Role of the JAK/STAT pathway in rat carotid artery remodeling after vascular injury. Circ Res. 2000;87:12-18.
38. Wang D, Liu Z, Li Q, Karpurapu M, Kundumani-Sridharan V, Cao H, Dronadula N, Rizvi F, Bajpai AK, Zhang C, Muller-Newen G, Harris KW, Rao GN. An essential role for gp130 in neointima formation following arterial injury. Circ Res. 2007;100:807-816.
39. Kovacic JC, Gupta R, Lee AC, Ma M, Fang F, Tolbert CN, Walts AD, Beltran LE, San H, Chen G, St Hilaire C, Boehm M. Stat3-dependent acute Rantes production in vascular smooth muscle cells modulates inflammation following arterial injury in mice. J Clin Invest. 2010;120: 303-314.
40. Leon ML, Zuckerman SH. Gamma interferon: a central mediator in atherosclerosis. Inflamm Res. 2005;54:395-411.
41. Zohlnhofer D, Richter T, Neumann F, Nuhrenberg T, Wessely R, Brandl R, Murr A, Klein CA, Baeuerle PA. Transcriptome analysis reveals a role of interferon-y in human neointima formation. Mol Cell. 2001;7: 1059-1069.
42. Kusaba K, Kai H, Koga M, Takayama N, Ikeda A, Yasukawa H, Seki Y, Egashira K, Imaizumi T. Inhibition of intrinsic interferon-y function prevents neointima formation after balloon injury. Hypertension. 2007; 49:909-915.
43. Maruyama I, Shigeta K, Miyahara H, Nakajima T, Shin H, Ide S, Kitajima I. Thrombin activates NF-KB through thrombin receptor and results in proliferation of vascular smooth muscle cells: role of thrombin in atherosclerosis and restenosis. Ann NY Acad Sci. 1997;811:429-436.
44. Wang Z, Castresana MR, Newman WH. Reactive oxygen species-sensitive p38 MAPK controls thrombin-induced migration of vascular smooth muscle cells. J Mol Cell Cardiol. 2004;36:49-56.
45. 2 expression is required for thrombin-induced vascular smooth muscle cell motility. J Biol Chem. 2005;280:3112-3120.