Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: The therapeutic potential of PARP inhibitors

Cardiovascular Drug Reviews

Volumn 25, Issue 3, 2007, Pages 235-260

  Pacher, Pál ^a   Szabó, Csaba ^b  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b RUTGERS NEW JERSEY MEDICAL SCHOOL   (United States)

Author keywords

Angiogenesis; Apoptosis; Cardiomyopathy; Diabetes; DNA repair; Heart failure; Inflammation; Necrosis; Nitric oxide; Peroxynitrite; Poly(ADP ribose) polymerase; Vascular remodeling

Indexed keywords

1,11B DIHYDRO[2H]BENZOPYRAN[4,3,2 D,E]ISOQUINOLIN 3 ONE; 1,5 DEHYDROXYISOQUINOLINE; 1,5 ISOQUINOLINEDIOL; 2 [(2 PIPERIDIN 1 YLETIL)THIO]QUINAZOLIN 4(3H) ONE; 2 [2 (1 PIPERIDINYL)ETHYLTHIO] 4(3H) QUINAZOLINONE; 3 AMINOBENZAMIDE; 3 NITROTYROSINE; 5 AMINOISOQUINOLINONE; 5 IODO 6 AMINO 1,2 BENZOPYRONE; ABT 888; ADENOSINE TRIPHOSPHATE; AG 014699; AUTACOID; BSI 201; ESTROGEN; GLP 21016; GPI 6150; INDUCIBLE NITRIC OXIDE SYNTHASE; INO 1001; KU 0059436; N (5,6 DIHYDRO 6 OXO 2 PHENANTHRIDINYL) 2 DIMETHYLAMINOACETAMIDE; NICOTINAMIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; O (2 HYDROXY 3 PIPERIDINOPROPYL)NICOTINIC AMIDOXIME; PHOSPHOTRANSFERASE; POLYAMINE; PURINE DERIVATIVE; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; TEMOZOLOMIDE; THIENO[2,3 C]ISOQUINOLIN 5 ONE; THYROID HORMONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VITAMIN D;

ABSENCE OF SIDE EFFECTS; ANGIOGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC CARDIOVASCULAR DISEASE; BONE MARROW SUPPRESSION; BREAST CANCER; CANCER; CARDIOGENIC SHOCK; CARDIOMYOPATHY; CELL DEATH; CLINICAL TRIAL; DIABETIC ANGIOPATHY; DNA DAMAGE; DNA REPAIR; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG FATALITY; DRUG INDICATION; DRUG MECHANISM; DRUG SAFETY; DRUG STRUCTURE; ELECTRON TRANSPORT; ENDOTHELIUM CELL; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INACTIVATION; GENE DELETION; GENE EXPRESSION; GLYCOLYSIS; HEART FAILURE; HEART INFARCTION; HEART INFARCTION PREVENTION; HEART INFARCTION SIZE; HEART MUSCLE CELL; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HEART VENTRICLE HYPERTROPHY; HEMORRHAGIC SHOCK; HUMAN; HYPERTENSION; INFLAMMATION; LIPID PEROXIDATION; MELANOMA; NITRATION; NITROSATIVE STRESS; NONHUMAN; OXIDATION; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN FUNCTION; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION; SOLID TUMOR; ST SEGMENT ELEVATION;

ANIMALS; CARDIOVASCULAR DISEASES; ENZYME INHIBITORS; HUMANS; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; POLY(ADP-RIBOSE) POLYMERASES;

EID: 35148896262     PISSN: 08975957     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1527-3466.2007.00018.x     Document Type: Review

References (162)

1. Aldinucci A, Gerlini G, Fossati S, Cipriani G, Ballerini C, Biagioli T, Pimpinelli N, Borgognoni L, Massacesi L, Moroni F, et al 2007) A key role for poly(ADP-ribose) polymerase-1 activity during human dendritic cell maturation. J Immunol 179 : 305 312.
2. Andrabi SA, Kim NS, Yu SW, Wang H, Koh DW, Sasaki M, Klaus JA, Otsuka T, Zhang Z, Koehler RC, et al 2006) Poly(ADP-ribose) (PAR) polymer is a death signal. Proc Nat Acad Sci USA 103 : 18308 18313.
3. Azevedo LC, Pedro MA, Souza LC, de Souza HP, Janiszewski M, da Luz PL, Laurindo FR (2000) Oxidative stress as a signaling mechanism of the vascular response to injury: The redox hypothesis of restenosis. Cardiovasc Res 47 : 436 445.
4. Bai P, Mabley JG, Liaudet L, Virag L, Szabo C, Pacher P (2004) Matrix metalloproteinase activation is an early event in doxorubicin-induced cardiotoxicity. Onco Rep 11 : 505 508.
5. Baker CS, Dutka DP, Pagano D, Rimoldi O, Pitt M, Hall RJ, Polak JM, Bonser RS, Camici PG (2002) Immunocytochemical evidence for inducible nitric oxide synthase and cyclooxygenase-2 expression with nitrotyrosine formation in human hibernating myocardium. Basic Res Cardiol 97 : 409 415.
6. Balakumar P, Singh M (2006) Possible role of poly(ADP-ribose) polymerase in pathological and physiological cardiac hypertrophy. Methods Findings Expl Clin Pharmacol 28 : 683 689.
7. Beller CJ, Radovits T, Kosse J, Gero D, Szabo C, Szabo G (2006) Activation of the peroxynitrite-poly(adenosine diphosphate-ribose) polymerase pathway during neointima proliferation: A new target to prevent restenosis after endarterectomy. J Vasc Surg 43 : 824 830.
8. Benko R, Pacher P, Vaslin A, Kollai M, Szabo C (2004) Restoration of the endothelial function in the aortic rings of apolipoprotein E deficient mice by pharmacological inhibition of the nuclear enzyme poly(ADP-ribose) polymerase. Life Sci 75 : 1255 1261.
9. Bhatnagar A (1997) Contribution of ATP to oxidative stress-induced changes in action potential of isolated cardiac myocytes. Am J Physiol 272 : H1598 1608.
10. Booz GW (2007) PARP inhibitors and heart failure - Translational medicine caught in the act. Congest Heart Fail 13 : 105 112.
11. Boulares HA, Giardina C, Navarro CL, Khairallah EA, Cohen SD (1999) Modulation of serum growth factor signal transduction in Hepa 1-6 cells by acetaminophen: An inhibition of c-myc expression, NF-kappaB activation, and Raf-1 kinase activity. Toxicol Sci 48 : 264 274.
12. Bowes J, McDonald MC, Piper J, Thiemermann C (1999) Inhibitors of poly (ADP-ribose) synthetase protect rat cardiomyocytes against oxidant stress. Cardiovasc Res 41 : 126 134.
13. Bowes J, Piper J, Thiemermann C (1998a) Inhibitors of the activity of poly (ADP-ribose) synthetase reduce the cell death caused by hydrogen peroxide in human cardiac myoblasts. Br J Pharmacol 124 : 1760 1766.
14. Bowes J, Ruetten H, Martorana PA, Stockhausen H, Thiemermann C (1998b) Reduction of myocardial reperfusion injury by an inhibitor of poly (ADP-ribose) synthetase in the pig. Eur J Pharmacol 359 : 143 150.
15. Cesselli D, Jakoniuk I, Barlucchi L, Beltrami AP, Hintze TH, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2001) Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circ Res 89 : 279 286.
16. Chong ZZ, Lin SH, Li F, Maiese K (2005) The sirtuin inhibitor nicotinamide enhances neuronal cell survival during acute anoxic injury through AKT, BAD, PARP, and mitochondrial associated "anti-apoptotic" pathways. Curr Neurovasc Res 2 : 271 285.
17. Csiszar A, Pacher P, Kaley G, Ungvari Z (2005) Role of oxidative and nitrosative stress, longevity genes and poly(ADP-ribose) polymerase in cardiovascular dysfunction associated with aging. Curr Vasc Pharmacol 3 : 285 291.
18. Dawson VL, Dawson TM (2004) Deadly conversations: Nuclear-mitochondrial cross-talk. J Bioenerg Biomembr 36 : 287 294.
19. Ditsworth D, Zong WX, Thompson CB (2007) Activation of poly(ADP)-ribose polymerase (PARP-1) induces release of the pro-inflammatory mediator HMGB1 from the nucleus. J Biol Chem 282 : 17845 17854.
20. Docherty JC, Kuzio B, Silvester JA, Bowes J, Thiemermann C (1999) An inhibitor of poly (ADP-ribose) synthetase activity reduces contractile dysfunction and preserves high energy phosphate levels during reperfusion of the ischaemic rat heart. Br J Pharmacol 127 : 1518 1524.
21. Donawho CK, Luo Y, Luo Y, Penning TD, Bauch JL, Bouska JJ, Bontcheva-Diaz VD, Cox BF, DeWeese TL, Dillehay LE, et al 2007) ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res 13 : 2728 2737.
22. Escobales N, Crespo MJ (2005) Oxidative-nitrosative stress in hypertension. Curr Vasc Pharmacol 3 : 231 246.
23. Evgenov OV, Liaudet L (2005) Role of nitrosative stress and activation of poly(ADP-ribose) polymerase-1 in cardiovascular failure associated with septic and hemorrhagic shock. Curr Vasc Pharmacol 3 : 293 299.
24. Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP (2006) NO-independent stimulators and activators of soluble guanylate cyclase: Discovery and therapeutic potential. Nat Rev Drug Discov 5 : 755 768.
25. Farivar AS, McCourtie AS, MacKinnon-Patterson BC, Woolley SM, Barnes AD, Chen M, Jagtap P, Szabo C, Salerno CT, Mulligan MS (2005) Poly (ADP) ribose polymerase inhibition improves rat cardiac allograft survival. Ann Thorac Surg 80 : 950 956.
26. Faro R, Toyoda Y, McCully JD, Jagtap P, Szabo E, Virag L, Bianchi C, Levitsky S, Szabo C, Sellke FW (2002) Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor. Ann Thorac Surg 73 : 575 581.
27. Feng Q, Lu X, Jones DL, Shen J, Arnold JM (2001) Increased inducible nitric oxide synthase expression contributes to myocardial dysfunction and higher mortality after myocardial infarction in mice. Circulation 104 : 700 704.
28. Ferdinandy P, Schulz R (2003) Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia-reperfusion injury and preconditioning. Br J Pharmacol 138 : 532 543.
29. Fiorillo C, Pace S, Ponziani V, Nediani C, Perna AM, Liguori P, Cecchi C, Nassi N, Donzelli GP, Formigli L, et al 2002) Poly(ADP-ribose) polymerase activation and cell injury in the course of rat heart heterotopic transplantation. Free Radic Res 36 : 79 87.
30. Fiorillo C, Ponziani V, Giannini L, Cecchi C, Celli A, Nassi N, Lanzilao L, Caporale R, Nassi P (2006) Protective effects of the PARP-1 inhibitor PJ34 in hypoxic-reoxygenated cardiomyoblasts. Cell Mol Life Sci 63 : 3061 3071.
31. Fiorillo C, Ponziani V, Giannini L, Cecchi C, Celli A, Nediani C, Perna AM, Liguori P, Nassi N, Formigli L, et al 2003) Beneficial effects of poly (ADP-ribose) polymerase inhibition against the reperfusion injury in heart transplantation. Free Radic Res 37 : 331 339.
32. Fong PC, Spicer J, Reade S, Reid A, Vidal L, Schellens JH, Tutt A, Harris PA, Kaye S, De Bono JS (2006) Phase I pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of a small molecule inhibitor of poly ADP-ribose polymerase (PARP), KU-0059436 (Ku) in patients (p) with advanced tumours. J Clin Oncol 24 : A3022.
33. Frye RA (1999) Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun 260 : 273 279.
34. Garcia Soriano F, Virag L, Jagtap P, Szabo E, Mabley JG, Liaudet L, Marton A, Hoyt DG, Murthy KG, Salzman AL, et al 2001) Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 7 : 108 113.
35. Gilad E, Zingarelli B, Salzman AL, Szabo C (1997) Protection by inhibition of poly (ADP-ribose) synthetase against oxidant injury in cardiac myoblasts In vitro. J Mol Cell Cardiol 29 : 2585 2597.
36. Graziani G, Szabo C 2005) Clinical perspectives of PARP inhibitors. Pharmacol Res 52 : 109 118.
37. Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: Role in cardiovascular biology and disease. Circ Res 86 : 494 501.
38. Grupp IL, Jackson TM, Hake P, Grupp G, Szabo C (1999) Protection against hypoxia-reoxygenation in the absence of poly (ADP-ribose) synthetase in isolated working hearts. J Mol Cell Cardiol 31 : 297 303.
39. Ha HC, Hester LD, Snyder SH (2002) Poly(ADP-ribose) polymerase-1 dependence of stress-induced transcription factors and associated gene expression in glia. Proc Natl Acad Sci USA 99 : 3270 3275.
40. Haince JF, Rouleau M, Hendzel MJ, Masson JY, Poirier GG (2005) Targeting poly(ADP-ribosyl)ation: A promising approach in cancer therapy. Trends Mol Med 11 : 456 463.
41. Halmosi R, Berente Z, Osz E, Toth K, Literati-Nagy P, Sumegi B (2001) Effect of poly(ADP-ribose) polymerase inhibitors on the ischemia-reperfusion- induced oxidative cell damage and mitochondrial metabolism in Langendorff heart perfusion system. Molec Pharmacol 59 : 1497 1505.
42. Harrison DG, Cai H, Landmesser U, Griendling KK (2003) Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease. J Renin Angiotensin Aldosterone Syst 4 : 51 61.
43. Hassa PO, Haenni SS, Elser M, Hottiger MO (2006) Nuclear ADP-ribosylation reactions in mammalian cells: Where are we today and where are we going? Microbiol Mol Biol Rev 70 : 789 829.
44. Hauser B, Groger M, Ehrmann U, Albicini M, Bruckner UB, Schelzig H, Venkatesh B, Li H, Szabo C, Speit G, et al 2006) The PARP-1 inhibitor INO-1001 facilitates hemodynamic stabilization without affecting DNA repair in porcine thoracic aortic cross-clamping-induced ischemia/reperfusion. Shock 25 : 633 640.
45. Hayashi Y, Sawa Y, Fukuyama N, Miyamoto Y, Takahashi T, Nakazawa H, Matsuda H (2003) Leukocyte-depleted terminal blood cardioplegia provides superior myocardial protective effects in association with myocardium-derived nitric oxide and peroxynitrite production for patients undergoing prolonged aortic crossclamping for more than 120 minutes. J Thorac Cardiovasc Surg 126 : 1813 1821.
46. Hayashi Y, Sawa Y, Ohtake S, Fukuyama N, Nakazawa H, Matsuda H (2001) Peroxynitrite formation from human myocardium after ischemia-reperfusion during open heart operation. Ann Thor Surg 72 : 571 576.
47. Inoue T, Kato T, Hikichi Y, Hashimoto S, Hirase T, Morooka T, Imoto Y, Takeda Y, Sendo F, Node K (2006) Stent-induced neutrophil activation is associated with an oxidative burst in the inflammatory process, leading to neointimal thickening. Thromb Haemost 95 : 43 48.
48. Jacobson GM, Dourron HM, Liu J, Carretero OA, Reddy DJ, Andrzejewski T, Pagano PJ (2003) Novel NAD(P)H oxidase inhibitor suppresses angioplasty-induced superoxide and neointimal hyperplasia of rat carotid artery. Circ Res 92 : 637 643.
49. Jagtap P, Soriano FG, Virag L, Liaudet L, Mabley J, Szabo E, Hasko G, Marton A, Lorigados CB, Gallyas F, et al 2002) Novel phenanthridinone inhibitors of poly (adenosine 5′-diphosphate-ribose) synthetase: Potent cytoprotective and antishock agents. Crit Care Med 30 : 1071 1082.
50. Jagtap P, Szabo C (2005) Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov 4 : 421 440.
51. Jagtap PG, Baloglu E, Southan GJ, Mabley JG, Li H, Zhou J, van Duzer J, Salzman AL, Szabo C (2005) Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. J Med Chem 48 : 5100 5103.
52. Jagtap PG, Southan GJ, Baloglu E, Ram S, Mabley JG, Marton A, Salzman A, Szabo C (2004) The discovery and synthesis of novel adenosine substituted 2,3-dihydro-1H-isoindol-1-ones: potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1). Bioorg Med Chem Lett 14 : 81 85.
53. Kooy NW, Lewis SJ, Royall JA, Ye YZ, Kelly DR, Beckman JS (1997) Extensive tyrosine nitration in human myocardial inflammation: Evidence for the presence of peroxynitrite. Crit Care Med 25 : 812 819.
54. Kummar S, Kinders R, Rubinstein L, Parchment RE, Murgo AJ, Collins J, Pickeral O, Low J, Steinberg SM, Gutierrez M, et al 2007) Compressing drug development timelines in oncology using phase '0' trials. Nat Rev Cancer 7 : 131 139.
55. Lapidus RG, Xu W, Spicer E, Hoover R, Zhang J (2006) PARP inhibitors enhance the effect of cisplatin against tumors and ameliorate cisplatin-induced neuropathy. Am Assoc Cancer Res 47 : A2141.
56. Levrand S, Vannay-Bouchiche C, Pesse B, Pacher P, Feihl F, Waeber B, Liaudet L (2006) Peroxynitrite is a major trigger of cardiomyocyte apoptosis in vitro and in vivo. Free Rad Biol Med 41 : 886 895.
57. Liaudet L, Soriano FG, Szabo E, Virag L, Mabley JG, Salzman AL, Szabo C (2000) Protection against hemorrhagic shock in mice genetically deficient in poly(ADP-ribose)polymerase. Proc Nat Acad Sci USA 97 : 10203 10208.
58. Liaudet L, Szabo E, Timashpolsky L, Virag L, Cziraki A, Szabo C (2001a) Suppression of poly (ADP-ribose) polymerase activation by 3-aminobenzamide in a rat model of myocardial infarction: Long-term morphological and functional consequences. Br J Pharmacol 133 : 1424 1430.
59. Liaudet L, Yang Z, Al-Affar EB, Szabo C (2001b) Myocardial ischemic preconditioning in rodents is dependent on poly (ADP-ribose) synthetase. Mol Med 7 : 406 417.
60. Lucchesi BR (1990) Modulation of leukocyte-mediated myocardial reperfusion injury. Ann Rev Pysiology 52 : 561 576.
61. Mabley JG, Soriano FG (2005) Role of nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic vascular dysfunction. Curr Vasc Pharmacol 3 : 247 252.
62. Mabley JG, Wallace R, Pacher P, Murphy K, Szabo C (2007) Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D. Int J Mol Med 19 : 947 952.
63. Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM (2002) Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques. Circulation 106 : 927 932.
64. Mason KA, Valdecanas D, Hunter NR, Milas L (2007) INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase, enhances tumor response to doxorubicin. Invest New Drugs in press.
65. Mehlhorn U, Krahwinkel A, Geissler HJ, LaRosee K, Fischer UM, Klass O, Suedkamp M, Hekmat K, Tossios P, Bloch W (2003) Nitrotyrosine and 8-isoprostane formation indicate free radical-mediated injury in hearts of patients subjected to cardioplegia. J Thorac Cardiovasc Surg 125 : 178 183.
66. Meyer RG, Meyer-Ficca ML, Whatcott CJ, Jacobson EL, Jacobson MK (2007) Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Exp Cell Res 313 : 2920 2936.
67. Mihm MJ, Coyle CM, Schanbacher BL, Weinstein DM, Bauer JA (2001) Peroxynitrite induced nitration and inactivation of myofibrillar creatine kinase in experimental heart failure. Cardiovasc Res 49 : 798 807.
68. Mihm MJ, Yu F, Weinstein DM, Reiser PJ, Bauer JA (2002) Intracellular distribution of peroxynitrite during doxorubicin cardiomyopathy: Evidence for selective impairment of myofibrillar creatine kinase. Br J Pharmacol 135 : 581 588.
69. Molnar A, Toth A, Bagi Z, Papp Z, Edes I, Vaszily M, Galajda Z, Papp JG, Varro A, Szuts V, et al 2006) Activation of the poly(ADP-ribose) polymerase pathway in human heart failure. Mol Med 12 : 143 152.
70. Morrow DA, Baran K, Krakover R, Dauerman H, Murphy SA, Kumar S, McCabe CH, Brickman CM, Salzman AL (2007) Safety, pharmacokinetics, and pharmacodynamics of a single intravenous administration of INO-1001 in subjects with ST-elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention: results of the TIMI 37A trial. J Am Coll Cardiol 2002A.
71. Muscoli C, Sacco I, Alecce W, Palma E, Nistico R, Costa N, Clementi F, Rotiroti D, Romeo F, Salvemini D, et al 2004) The protective effect of superoxide dismutase mimetic M40401 on balloon injury-related neointima formation: Role of the lectin-like oxidized low-density lipoprotein receptor-1. J Pharmacol Exp Ther 311 : 44 50.
72. Obrosova IG, Minchenko AG, Frank RN, Seigel GM, Zsengeller Z, Pacher P, Stevens MJ, Szabo C (2004) Poly(ADP-ribose) polymerase inhibitors counteract diabetes- and hypoxia-induced retinal vascular endothelial growth factor overexpression. Int J Mol Med 14 : 55 64.
73. Oliver FJ, Menissier-de Murcia J, Nacci C, Decker P, Andriantsitohaina R, Muller S, de la Rubia G, Stoclet JC, de Murcia G (1999) Resistance to endotoxic shock as a consequence of defective NF-kappaB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J 18 : 4446 4454.
74. Oumouna-Benachour K, Hans CP, Suzuki Y, Naura A, Datta R, Belmadani S, Fallon K, Woods C, Boulares AH (2007) Poly(ADP-Ribose) polymerase inhibition reduces atherosclerotic plaque size and promotes factors of plaque stability in apolipoprotein e-deficient mice. Effects on macrophage recruitment, nuclear factor-{kappa}b nuclear translocation, and foam cell death. Circulation 115 (18 2442 2450.
75. Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87 : 315 424.
76. Pacher P, Cziraki A, Mabley JG, Liaudet L, Papp L, Szabo C (2002a) Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents. Biochem Pharmacol 64 : 1785 1791.
77. Pacher P, Liaudet L, Bai P, Mabley JG, Kaminski PM, Virag L, Deb A, Szabo E, Ungvari Z, Wolin MS, et al 2003) Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction. Circulation 107 : 896 904.
78. Pacher P, Liaudet L, Bai P, Virag L, Mabley JG, Hasko G, Szabo C (2002b) Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure. J Pharmacol Exp Ther 300 : 862 867.
79. Pacher P, Liaudet L, Mabley JG, Cziraki A, Hasko G, Szabo C (2006a) Beneficial effects of a novel ultrapotent poly(ADP-ribose) polymerase inhibitor in murine models of heart failure. Int J Mol Med 17 : 369 375.
80. Pacher P, Liaudet L, Mabley J, Komjati K, Szabo C (2002c) Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure. J Am Coll Cardiol 40 : 1006 1016.
81. Pacher P, Liaudet L, Soriano FG, Mabley JG, Szabo E, Szabo C (2002d) The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. Diabetes 51 : 514 521.
82. Pacher P, Mabley JG, Liaudet L, Evgenov OV, Marton A, Hasko G, Kollai M, Szabo C (2004a) Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure. Am J Physiol Heart Circ Physiol 287 : H2132 2137.
83. Pacher P, Mabley JG, Soriano FG, Liaudet L, Komjati K, Szabo C (2002e) Endothelial dysfunction in aging animals: The role of poly(ADP-ribose) polymerase activation. Br J Pharmacol 135 : 1347 1350.
84. Pacher P, Mabley JG, Soriano FG, Liaudet L, Szabo C (2002f) Activation of poly(ADP-ribose) polymerase contributes to the endothelial dysfunction associated with hypertension and aging. Int J Mol Med 9 : 659 664.
85. Pacher P, Nivorozhkin A, Szabo C (2006b) Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58 : 87 114.
86. Pacher P, Obrosova IG, Mabley JG, Szabo C (2005a) Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies. Curr Med Chem 12 : 267 275.
87. Pacher P, Schulz R, Liaudet L, Szabo C (2005b) Nitrosative stress and pharmacological modulation of heart failure. Trends Pharmacol Sci 26 : 302 310.
88. Pacher P, Szabo C (2005) Role of poly(ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: Endothelial dysfunction, as a common underlying theme. Antioxid Redox Signal 7 : 1568 1580.
89. Pacher P, Szabo C (2006) Role of peroxynitrite in the pathogenesis of cardiovascular complications of diabetes. Curr Opin Pharmacol 6 : 136 141.
90. Pacher P, Vaslin A, Benko R, Mabley JG, Liaudet L, Hasko G, Marton A, Batkai S, Kollai M, Szabo C (2004b) A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging. J Pharmacol Exp Ther 311 : 485 491.
91. Palfi A, Toth A, Hanto K, Deres P, Szabados E, Szereday Z, Kulcsar G, Kalai T, Hideg K, Gallyas F, et al 2006) PARP inhibition prevents postinfarction myocardial remodeling and heart failure via the protein kinase C/glycogen synthase kinase-3beta pathway. J Mol Cell Cardiol 41 : 149 159.
92. Pieper AA, Walles T, Wei G, Clements EE, Verma A, Snyder SH, Zweier JL (2000) Myocardial postischemic injury is reduced by polyADPripose polymerase-1 gene disruption. Mol Med 6 : 271 282.
93. Pillai JB, Gupta M, Rajamohan SB, Lang R, Raman J, Gupta MP (2006) Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II-induced cardiac hypertrophy. Am J Physiol Heart Circ Physiol 291 : H1545 1553.
94. + depletion and reduced Sir2alpha deacetylase activity. J Biol Chem 280 : 43121 43130.
95. Pillai JB, Russell HM, Raman J, Jeevanandam V, Gupta MP (2005b) Increased expression of poly(ADP-ribose) polymerase-1 contributes to caspase-independent myocyte cell death during heart failure. Am J Physiol Heart Circ Physiol 288 : H486 496.
96. Plummer ER (2006) Inhibition of poly(ADP-ribose) polymerase in cancer. Curr Opin Pharmacol 6 : 364 368.
97. Plummer R, Lorigan P, Evans J, Steven N, Middleton M, Wilson R, Snow K, Dewji R, Calvert H (2006) First and final report of a phase II study of the poly(ADP-ribose) polymerase (PARP) inhibitor, AG014699, in combination with temozolomide (TMZ) in patients with metastatic malignant melanoma (MM). J Clin Oncol 24 : A8013.
98. Poitras MF, Koh DW, Yu SW, Andrabi SA, Mandir AS, Poirier GG, Dawson VL, Dawson TM (2007) Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Neuroscience 148 : 198 211.
99. Radovits T, Seres L, Gero D, Berger I, Szabo C, Karck M, Szabo G (2007) Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction. Exp Gerontol 42 : 676 685.
100. Rajesh M, Mukhopadhyay P, Batkai S, Godlewski G, Hasko G, Liaudet L, Pacher P (2006a) Pharmacological inhibition of poly(ADP-ribose) polymerase inhibits angiogenesis. Biochem Biophys Res Commun 350 : 352 357.
101. Rajesh M, Mukhopadhyay P, Godlewski G, Batkai S, Hasko G, Liaudet L, Pacher P (2006b) Poly(ADP-ribose)polymerase inhibition decreases angiogenesis. Biochem Biophys Res Commun 350 : 1056 1062.
102. Ratnam K, Low JA (2007) Current development of clinical inhibitors of poly(ADP-ribose) polymerase in oncology. Clin Cancer Res 13 : 1383 1388.
103. Ravalli S, Albala A, Ming M, Szabolcs M, Barbone A, Michler RE, Cannon PJ (1998) Inducible nitric oxide synthase expression in smooth muscle cells and macrophages of human transplant coronary artery disease. Circulation 97 : 2338 2345.
104. Rubbo H, O'Donnell V (2005) Nitric oxide, peroxynitrite and lipoxygenase in atherogenesis: Mechanistic insights. Toxicology 208 : 305 317.
105. Schreiber V, Dantzer F, Ame JC, de Murcia G (2006) Poly(ADP-ribose): Novel functions for an old molecule. Nat Rev Mol Cell Biol 7 : 517 528.
106. Schulz R (2007) Intracellular targets of matrix metalloproteinase-2 in cardiac disease: Rationale and therapeutic approaches. Ann Rev Pharmacol Toxicol 47 : 211 242.
107. Soriano FG, Liaudet L, Szabo E, Virag L, Mabley JG, Pacher P, Szabo C (2002) Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice. Shock 17 : 286 292.
108. Soriano FG, Nogueira AC, Caldini EG, Lins MH, Teixeira AC, Cappi SB, Lotufo PA, Bernik MM, Zsengeller Z, Chen M et al 2006) Potential role of poly(adenosine 5-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock. Crit Care Med 34 : 1073 1079.
109. Soriano FG, Pacher P, Mabley J, Liaudet L, Szabo C (2001) Rapid reversal of the diabetic endothelial dysfunction by pharmacological inhibition of poly(ADP-ribose) polymerase. Circ Res 89 : 684 691.
110. Southan GJ, Szabo C (2003) Poly(ADP-ribose) polymerase inhibitors. Curr Med Chem 10 : 321 340.
111. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, et al 1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397 : 441 446.
112. Szabados E, Literati-Nagy P, Farkas B, Sumegi B (2000) BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase. Biochem Pharmacol 59 : 937 945.
113. Szabo A, Hake P, Salzman AL, Szabo C (1998) 3-Aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, improves hemodynamics and prolongs survival in a porcine model of hemorrhagic shock. Shock 10 : 347 353.
114. Szabo C (1998) Potential role of the peroxynitrate-poly(ADP-ribose) synthetase pathway in a rat model of severe hemorrhagic shock. Shock 9 : 341 344.
115. Szabo C (2003) Multiple pathways of peroxynitrite cytotoxicity. Toxicol Lett 140-141 : 105 112.
116. Szabo C (2005a) Cardioprotective effects of poly(ADP-ribose) polymerase inhibition. Pharmacol Res 52 : 34 43.
117. Szabo C (2005b) Pharmacological inhibition of poly(ADP-ribose) polymerase in cardiovascular disorders: Future directions. Curr Vasc Pharmacol 3 : 301 303.
118. Szabo C (2005c) Roles of poly(ADP-ribose) polymerase activation in the pathogenesis of diabetes mellitus and its complications. Pharmacol Res 52 : 60 71.
119. Szabo C (2006) Poly(ADP-ribose) polymerase activation by reactive nitrogen species-relevance for the pathogenesis of inflammation. Nitric Oxide 14 : 169 179.
120. Szabo C (2007) Poly (ADP-ribose) polymerase activation and circulatory shock. Novartis Found Symp 280 : 92 103 discussion 103-107, 160-164.
121. Szabo C, Billiar TR (1999) Novel roles of nitric oxide in hemorrhagic shock. Shock 12 : 1 9.
122. Szabo C, Cuzzocrea S, Zingarelli B, O'Connor M, Salzman AL (1997) Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J Clin Invest 100 : 723 735.
123. Szabo C, Pacher P, Swanson RA (2006a) Novel modulators of poly(ADP-ribose) polymerase. Trends Pharmacol Sci 27 : 626 630.
124. Szabo C, Pacher P, Zsengeller Z, Vaslin A, Komjati K, Benko R, Chen M, Mabley JG, Kollai M (2004a) Angiotensin II-mediated endothelial dysfunction: Role of poly(ADP-ribose) polymerase activation. Mol Med 10 : 28 35.
125. Szabo C, Zanchi A, Komjati K, Pacher P, Krolewski AS, Quist WC, LoGerfo FW, Horton ES, Veves A (2002a) Poly(ADP-ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity. Circulation 106 : 2680 2686.
126. Szabo G, Bahrle S (2005) Role of nitrosative stress and poly(ADP-ribose) polymerase activation in myocardial reperfusion injury. Curr Vasc Pharmacol 3 : 215 220.
127. Szabo G, Bahrle S, Sivanandam V, Stumpf N, Gero D, Berger I, Beller C, Hagl S, Szabo C, Dengler TJ (2006b) Immunomodulatory effects of poly(ADP-ribose) polymerase inhibition contribute to improved cardiac function and survival during acute cardiac rejection. J Heart Lung Transplant 25 : 794 804.
128. Szabo G, Bahrle S, Stumpf N, Sonnenberg K, Szabo EE, Pacher P, Csont T, Schulz R, Dengler TJ, Liaudet L, et al 2002b) Poly(ADP-ribose) polymerase inhibition reduces reperfusion injury after heart transplantation. Circ Res 90 : 100 106.
129. Szabo G, Bahrle S, Stumpf N, Szabo C, Hagl S (2006c) Contractile dysfunction in experimental cardiac allograft rejection: role of the poly (ADP-ribose) polymerase pathway. Transpl Int 19 : 506 513.
130. Szabo G, Soos P, Bahrle S, Zsengeller Z, Flechtenmacher C, Hagl S, Szabo C (2004b) Role of poly(ADP-ribose) polymerase activation in the pathogenesis of cardiopulmonary dysfunction in a canine model of cardiopulmonary bypass. Eur J Cardiothorac Surg 25 : 825 832.
131. Szabo G, Soos P, Heger U, Flechtenmacher C, Bahrle S, Zsengeller Z, Szabo C, Hagl S (2005) Poly(ADP-ribose) polymerase inhibition attenuates biventricular reperfusion injury after orthotopic heart transplantation. Eur J Cardiothorac Surg 27 : 226 234.
132. Szabo G, Soos P, Mandera S, Heger U, Flechtenmacher C, Bahrle S, Seres L, Cziraki A, Gries A, Zsengeller Z, et al 2004c) INO-1001 a novel poly(ADP-ribose) polymerase (PARP) inhibitor improves cardiac and pulmonary function after crystalloid cardioplegia and extracorporal circulation. Shock 21 : 426 432.
133. Szabolcs MJ, Ravalli S, Minanov O, Sciacca RR, Michler RE, Cannon PJ (1998) Apoptosis and increased expression of inducible nitric oxide synthase in human allograft rejection. Transplantation 65 : 804 812.
134. Szenczi O, Kemecsei P, Holthuijsen MF, van Riel NA, van der Vusse GJ, Pacher P, Szabo C, Kollai M, Ligeti L, Ivanics T (2005) Poly(ADP-ribose) polymerase regulates myocardial calcium handling in doxorubicin-induced heart failure. Biochem Pharmacol 69 : 725 732.
135. Tasatargil A, Dalaklioglu S, Sadan G (2005) Inhibition of poly(ADP-ribose) polymerase prevents vascular hyporesponsiveness induced by lipopolysaccharide in isolated rat aorta. Pharmacol Res 51 : 581 586.
136. Tentori L, Graziani G (2005) Chemopotentiation by PARP inhibitors in cancer therapy. Pharmacol Res 52 : 25 33.
137. Tentori L, Leonetti C, Scarsella M, D'Amati G, Vergati M, Portarena I, Xu W, Kalish V, Zupi G, Zhang J, et al. (2003) Systemic administration of GPI 15427, a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin Cancer Res 9 : 5370 5379.
138. Thiemermann C, Bowes J, Myint FP, Vane JR (1997) Inhibition of the activity of poly(ADP ribose) synthetase reduces ischemia-reperfusion injury in the heart and skeletal muscle. Proc Nat Acad Sci USA 94 : 679 683.
139. Thomas HD, Calabrese CR, Batey MA, Canan S, Hostomsky Z, Kyle S, Maegley KA, Newell DR, Skalitzky D, Wang LZ, et al 2007) Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther 6 : 945 956.
140. Toth-Zsamboki E, Horvath E, Vargova K, Pankotai E, Murthy K, Zsengeller Z, Barany T, Pek T, Fekete K, Kiss RG, et al 2006) Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes. Mol Med 12 : 221 228.
141. Turko IV, Murad F (2002) Protein nitration in cardiovascular diseases. Pharmacol Rev 54 : 619 634.
142. Ungvari Z, Gupte SA, Recchia FA, Batkai S, Pacher P (2005) Role of oxidative-nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure. Curr Vasc Pharmacol 3 : 221 229.
143. Veres B, Gallyas F Jr., Varbiro G, Berente Z, Osz E, Szekeres G, Szabo C, Sumegi B (2003) Decrease of the inflammatory response and induction of the Akt/protein kinase B pathway by poly-(ADP-ribose) polymerase 1 inhibitor in endotoxin-induced septic shock. Biochem Pharmacol 65 : 1373 1382.
144. Virag L (2005) Structure and function of poly(ADP-ribose) polymerase-1: Role in oxidative stress-related pathologies. Curr Vasc Pharmacol 3 : 209 214.
145. Virag L, Szabo C (2002) The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 54 : 375 429.
146. Virag L, Szabo E, Gergely P, Szabo C (2003) Peroxynitrite-induced cytotoxicity: Mechanism and opportunities for intervention. Toxicol Lett 140-141 : 113 124.
147. Wang C, Bedikian AY, Kim K, Papadopoulos NE, Hwu W, Hwu P (2006)
148. Wayman N, McDonald MC, Thompson AS, Threadgill MD, Thiemermann C (2001) 5-aminoisoquinolinone, a potent inhibitor of poly (adenosine 5′-diphosphate ribose) polymerase, reduces myocardial infarct size. Eur J Pharmacol 430 : 93 100.
149. Weinstein DM, Mihm MJ, Bauer JA (2000) Cardiac peroxynitrite formation and left ventricular dysfunction following doxorubicin treatment in mice. J Pharmacol Exper Ther 294 : 396 401.
150. Woon EC, Threadgill MD (2005) Poly(ADP-ribose)polymerase inhibition - where now? Curr Med Chem 12 : 2373 2392.
151. Xiao CY, Chen M, Zsengeller Z, Li H, Kiss L, Kollai M, Szabo C (2005) Poly(ADP-Ribose) polymerase promotes cardiac remodeling, contractile failure, and translocation of apoptosis-inducing factor in a murine experimental model of aortic banding and heart failure. J Pharmacol Exper Ther 312 : 891 898.
152. Xiao CY, Chen M, Zsengeller Z, Szabo C (2004) Poly(ADP-ribose) polymerase contributes to the development of myocardial infarction in diabetic rats and regulates the nuclear translocation of apoptosis-inducing factor. J Pharmacol Exper Ther 310 : 498 504.
153. Xu Y, Huang S, Liu ZG, Han J (2006) Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1/TRAF2-mediated JNK1 activation. J Biol Chem 281 : 8788 8795.
154. Yang Z, Zingarelli B, Szabo C (2000) Effect of genetic disruption of poly (ADP-ribose) synthetase on delayed production of inflammatory mediators and delayed necrosis during myocardial ischemia-reperfusion injury. Shock 13 : 60 66.
155. Yu SW, Andrabi SA, Wang H, Kim NS, Poirier GG, Dawson TM, Dawson VL (2006) Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death. Proc Nat Acad Sci USA 103 : 18314 18319.
156. Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297 : 259 263.
157. Zhou HZ, Swanson RA, Simonis U, Ma X, Cecchini G, Gray MO (2006) Poly(ADP-ribose) polymerase-1 hyperactivation and impairment of mitochondrial respiratory chain complex I function in reperfused mouse hearts. Am J Physiol Heart Circ Physiol 291 : H714 723.
158. Zingarelli B, Cuzzocrea S, Zsengeller Z, Salzman AL, Szabo C (1997) Protection against myocardial ischemia and reperfusion injury by 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase. Cardiovasc Res 36 : 205 215.
159. Zingarelli B, Hake PW, Burroughs TJ, Piraino G, O'Connor M, Denenberg A (2004a) Activator protein-1 signalling pathway and apoptosis are modulated by poly(ADP-ribose) polymerase-1 in experimental colitis. Immunology 113 : 509 517.
160. Zingarelli B, Hake PW, O'Connor M, Denenberg A, Kong S, Aronow BJ (2003) Absence of poly(ADP-ribose)polymerase-1 alters nuclear factor-kappa B activation and gene expression of apoptosis regulators after reperfusion injury. Mol Med 9 : 143 153.
161. Zingarelli B, Hake PW, O'Connor M, Denenberg A, Wong HR, Kong S, Aronow BJ (2004b) Differential regulation of activator protein-1 and heat shock factor-1 in myocardial ischemia and reperfusion injury: Role of poly(ADP-ribose) polymerase-1. Am J Physiol Heart Circ Physiol 286 : H1408 1415.
162. Zingarelli B, Salzman AL, Szabo C (1998) Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res 83 : 85 94.