Phosphodiesterases as targets for intermittent claudication

Handbook of Experimental Pharmacology

Volumn 204, Issue , 2011, Pages 211-236

  Liu, Yongge ^a   Shakur, Yasmin ^a   Kambayashi, Junichi ^a  

^a OTSUKA PHARMACEUTICAL DEVELOPMENT AND COMMERCIALIZATION INC   (United States)

Author keywords

Adenosine; Atherosclerosis; Cilostazol; Intermittent claudication; Peripheral arterial disease; Phosphodiesterase

Indexed keywords

ACETYLSALICYLIC ACID; ADENOSINE; ANTITHROMBOCYTIC AGENT; ATACIGUAT; BERAPROST; CALCIUM CHANNEL BLOCKING AGENT; CARNITINE; CILOSTAMIDE; CILOSTAZOL; CLOPIDOGREL; CYCLIC AMP; CYCLIC GMP; ENOXAMIDE; GLYCOPROTEIN VI; HMR 1766; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ILOPROST; K 134; LIPID; MILRINONE; NITRIC OXIDE; OPC 33509; PAPAVERINE; PAROGRELIL; PENTOXIFYLLINE; PHOSPHODIESTERASE; PHOSPHODIESTERASE III INHIBITOR; PHOSPHODIESTERASE INHIBITOR; PLACEBO; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADIPOCYTE; ANKLE BRACHIAL INDEX; ANTIPLATELET ACTIVITY; ARTICLE; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; BLEEDING; BLOOD PRESSURE REGULATION; BRAIN INFARCTION; CARDIOVASCULAR RISK; COMBINATION CHEMOTHERAPY; DIFFERENTIAL DIAGNOSIS; DISEASE ASSOCIATION; DRUG ACTIVITY; DRUG EFFICACY; DRUG STRUCTURE; DRUG SYNTHESIS; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM; ENZYME INHIBITION; EXERCISE; HEART FUNCTION; HEART INFARCTION SIZE; HUMAN; IC 50; INTERMITTENT CLAUDICATION; ISCHEMIA; LIFESTYLE MODIFICATION; LIPID METABOLISM; MACROPHAGE; MONOTHERAPY; MORBIDITY; MORTALITY; MUSCLE BLOOD FLOW; MUSCLE METABOLISM; NONHUMAN; PATHOPHYSIOLOGY; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; QUALITY OF LIFE; REPERFUSION INJURY; RESTENOSIS; RISK REDUCTION; SMOKING CESSATION; SMOOTH MUSCLE FIBER; SYSTOLIC BLOOD PRESSURE; THROMBOCYTE; TREADMILL EXERCISE; TREATMENT RESPONSE; VASCULAR SMOOTH MUSCLE; VASODILATATION; WALKING; DRUG DEVELOPMENT; ENZYMOLOGY; PHYSIOLOGY; REVIEW; VASCULAR ENDOTHELIUM;

ATHEROSCLEROSIS; BLOOD PLATELETS; DRUG DISCOVERY; ENDOTHELIUM, VASCULAR; HUMANS; INTERMITTENT CLAUDICATION; MUSCLE, SMOOTH, VASCULAR; NITRIC OXIDE; PHOSPHODIESTERASE INHIBITORS; PHOSPHORIC DIESTER HYDROLASES;

EID: 79960912304     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-17969-3_9     Document Type: Article

References (131)

1. Ambrus JL, Ambrus CM, Taheri SA, Gastpar H, Reddington MM, Taheri P, Kahn EA, Schattman GL, Dean LS, Moore RH (1984) Red cell flexibility and platelet aggregation in patients with chronic obstructive vascular disease (COAD) and study of therapeutic approaches. Angiology 35:418-426 (Pubitemid 14066492)
2. Ashikaga T, Strada SJ, Thompson WJ (1997) Altered expression of cyclic nucleotide phosphodiesterase isozymes during culture of aortic endothelial cells. Biochem Pharmacol 54:1071-1079 (Pubitemid 27479020)
3. Askew CD, Green S, Walker PJ, Kerr GK, Green AA, Williams AD, Febbraio MA (2005) Skeletal muscle phenotype is associated with exercise tolerance in patients with peripheral arterial disease. J Vasc Surg 41:802-807 (Pubitemid 40693802)
4. Barker GA, Green S, Askew CD, Green AA, Walker PJ (2001) Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease. Med Sci Sports Exerc 33:1415-1422 (Pubitemid 32831429)
5. Barton M, Haudenschild CC (2001) Endothelium and atherogenesis: endothelial therapy revisited. J Cardiovasc Pharmacol 38(Suppl 2):S23-S25
6. Beebe HG, Dawson DL, Cutler BS, Herd JA, Strandness DEJ, Bortey EB, Forbes WP (1999) A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med 159:2041-2050 (Pubitemid 29453592)
7. Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58:488-520 (Pubitemid 44394910)
8. Berman W Jr, Berman N, Pathak D, Wood SC (1994) Effects of pentoxifylline (Trental) on blood flow, viscosity, and oxygen transport in young adults with inoperable cyanotic congenital heart disease. Pediatr Cardiol 15:66-70 (Pubitemid 24091992)
9. Boger RH, Bode-Boger SM, Thiele W, Creutzig A, Alexander K, Frolich JC (1998) Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol 32:1336-1344
10. Brass EP, Anthony R, Cobb FR, Koda I, Jiao J, Hiatt WR (2006) The novel phosphodiesterase inhibitor NM-702 improves claudication-limited exercise performance in patients with peripheral arterial disease. J Am Coll Cardiol 48:2539-2545 (Pubitemid 44881218)
11. Bregar U, Poredos P, Sabovic M, Jug B, Sebestjen M (2009) The influence of atorvastatin on walking performance in peripheral arterial disease. Vasa 38:155-159
12. Cheung P, Yang G, Boden G (2003) Milrinone, a selective phosphodiesterase 3 inhibitor, stimulates lipolysis, endogenous glucose production, and insulin secretion. Metabolism 52: 1496-1500 (Pubitemid 37461121)
13. Chiu PJ, Vemulapalli S, Chintala M, Kurowski S, Tetzloff GG, Brown AD, Sybertz EJ (1997) Inhibition of platelet adhesion and aggregation by E4021, a type V phosphodiesterase inhibitor, in guinea pigs. Naunyn Schmiedebergs Arch Pharmacol 355:463-469 (Pubitemid 27140471)
14. Choi JM, Shin HK, Kim KY, Lee JH, HongKW(2002) Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats. J Pharmacol Exp Ther 300:787-793 (Pubitemid 34164980)
15. Choi YH, Park S, Hockman S, Zmuda-Trzebiatowska E, Svennelid F, Haluzik M, Gavrilova O, Ahmad F, Pepin L, Napolitano M, Taira M, Sundler F, Stenson HL, Degerman E, Manganiello VC (2006) Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice. J Clin Invest 116:3240-3251 (Pubitemid 44878638)
16. Conti M, Beavo J (2007) Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem 76:481-511
17. Creager MA, Pande RL, Hiatt WR (2008) A randomized trial of iloprost in patients with intermittent claudication. Vasc Med 13:5-13 (Pubitemid 351596923)
18. Dal LA, De MD, Flore R, Gaetani E, Gasbarrini A, Gerardino L, Pola R, Santoliquido A, Serricchio M, Tondi P, Nolfe G (1999) Effects of propionyl-L-carnitine on peripheral arterial obliterative disease of the lower limbs: a double-blind clinical trial. Drugs Exp Clin Res 25:29-36 (Pubitemid 29199590)
19. Dawson DL, Cutler BS, Meissner MH, Strandness DEJ (1998) Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. Circulation 98:678-686 (Pubitemid 28387495)
20. Dawson DL, Cutler BS, Hiatt WR, Hobson RW, Martin JD, Bortey EB, Forbes WP, Strandness DE (2000) A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 109:523-530
21. Dawson DL, Zheng Q, Worthy SA, Charles B, Bradley DV Jr (2002) Failure of pentoxifylline or cilostazol to improve blood and plasma viscosity, fibrinogen, and erythrocyte deformability in claudication. Angiology 53:509-520
22. de la Cruz JP, Romero MM, Sanchez P, de la Sanchez CF (1993) Antiplatelet effect of pentoxifylline in human whole blood. Gen Pharmacol 24:605-609 (Pubitemid 23179234)
23. Dimmeler S, Haendeler J, Galle J, Zeiher AM (1997) Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-like proteases: a mechanistic clue to the response to injury hypothesis. Circulation 95:1760-1763 (Pubitemid 27164389)
24. Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, Grines CL, Block E, Ghazzal ZM, Morris DC, Liberman H, Parker K, Jurkovitz C, Murrah N, Foster J, Hyde P, Mancini GB, Weintraub WS (2005) Coronary stent restenosis in patients treated with cilostazol. Circulation 112:2826-2832 (Pubitemid 41641677)
25. Dunkel B, Rickards KJ, Page CP, Cunningham FM (2007) Phosphodiesterase isoenzymes in equine platelets and their influence on platelet adhesion. Am J Vet Res 68:1354-1360 (Pubitemid 350267966)
26. Dunkern TR, Hatzelmann A (2005) The effect of Sildenafil on human platelet secretory function is controlled by a complex interplay between phosphodiesterases 2, 3 and 5. Cell Signal 17:331-339 (Pubitemid 39574694)
27. Ehrly AM (1978) The effect of pentoxifylline on the flow properties of human blood. Curr Med Res Opin 5:608-613 (Pubitemid 9024528)
28. Elam MB, Heckman J, Crouse JR, Hunninghake DB, Herd JA, Davidson M, Gordon IL, Bortey EB, Forbes WP (1998) Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. Arterioscler Thromb Vasc Biol 18:1942-1947 (Pubitemid 28565758)
29. Ferraresi I, Bozzini F, Torta D, Frigerio R, Bernasconi C, Agostoni A (1983) In vitro effects of pentoxifylline on hemoglobin affinity for oxygen and electrolytic equilibrium of human blood. Ric Clin Lab 13:459-465 (Pubitemid 14220850)
30. Fischmeister R, Castro LR, bi-Gerges A, Rochais F, Jurevicius J, Leroy J, Vandecasteele G (2006) Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases. Circ Res 99:816-828 (Pubitemid 44556380)
31. Fong M, Yoshitake M, Kambayashi J, Liu Y (2010) Cilostazol increases tissue blood flow in contracting rabbit gastrocnemius muscle. Circ J 74:181-187
32. Frantz S (2005) Drug discovery: playing dirty. Nature 437:942-943
33. Fukasawa M, Nishida H, Sato T, Miyazaki M, Nakaya H (2008) 6-[4-(1-Cyclohexyl-1Htetrazol-5-yl)butoxy]-3, 4-dihydro-2-(1H)quinolinone (cilostazol), a phosphodiesterase type 3 inhibitor, reduces infarct size via activation of mitochondrial Ca2+-activated K+ channels in rabbit hearts. J Pharmacol Exp Ther 326:100-104 (Pubitemid 351872116)
34. Galle J, Lehmann-Bodem C, Hubner U, Heinloth A, Wanner C (2000) CyA and OxLDL cause endothelial dysfunction in isolated arteries through endothelin-mediated stimulation of O2-formation. Nephrol Dial Transplant 15:339-346 (Pubitemid 30116468)
35. Girolami B, Bernardi E, Prins MH, Ten Cate JW, Hettiarachchi R, Prandoni P, Girolami A, Buller HR (1999) Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis. Arch Intern Med 159:337-345 (Pubitemid 29091621)
36. Goto S (2005) Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atheroscler Suppl 6:3-11 (Pubitemid 43263084)
37. Greenhaff PL, Campbell-OSullivan SP, Constantin-Teodosiu D, Poucher SM, Roberts PA, Timmons JA (2004) Metabolic inertia in contracting skeletal muscle: a novel approach for pharmacological intervention in peripheral vascular disease. Br J Clin Pharmacol 57: 237-243 (Pubitemid 38296986)
38. Gudmundsdottir IJ, McRobbie SJ, Robinson SD, Newby DE, Megson IL (2005) Sildenafil potentiates nitric oxide mediated inhibition of human platelet aggregation. Biochem Biophys Res Commun 337:382-385 (Pubitemid 41393806)
39. Hambleton R, Krall J, Tikishvili E, Honeggar M, Ahmad F, Manganiello VC, Movsesian MA (2005) Isoforms of cyclic nucleotide phosphodiesterase PDE3 and their contribution to cAMP hydrolytic activity in subcellular fractions of human myocardium. J Biol Chem 280:39168-39174 (Pubitemid 41713868)
40. Hankey GJ, Norman PE, Eikelboom JW (2006) Medical treatment of peripheral arterial disease. JAMA 295:547-553 (Pubitemid 43200349)
41. Hashimoto A, Miyakoda G, Hirose Y, Mori T (2006) Activation of endothelial nitric oxide synthase by cilostazol via a cAMP/protein kinase A-and phosphatidylinositol 3-kinase/Aktdependent mechanism. Atherosclerosis 189:350-357 (Pubitemid 44634499)
42. Hiatt WR (2001) Medical treatment of peripheral arterial disease and claudication. N Engl J Med 344:1608-1621 (Pubitemid 32479915)
43. Hiatt WR (2004) Carnitine and peripheral arterial disease. Ann NY Acad Sci 1033:92-98 (Pubitemid 39656741)
44. Hiatt WR, Regensteiner JG, Creager MA, Hirsch AT, Cooke JP, Olin JW, Gorbunov GN, Isner J, Lukjanov YV, Tsitsiashvili MS, Zabelskaya TF, Amato A (2001) Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication. Am J Med 110:616-622 (Pubitemid 32510688)
45. Hiatt WR, Money SR, Brass EP (2008) Long-term safety of cilostazol in patients with peripheral artery disease: the CASTLE study (Cilostazol: A Study in Long-term Effects). J Vasc Surg 47:330-336
46. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WRC, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA (2006) ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic). Circulation 113:e463-e465
47. Honda F, Imai H, Ishikawa M, Kubota C, Shimizu T, Fukunaga M, Saito N (2006) Cilostazol attenuates gray and white matter damage in a rodent model of focal cerebral ischemia. Stroke 37:223-228 (Pubitemid 43732075)
48. Igawa T, Tani T, Chijiwa T, Shiragiku T, Shimidzu S, Kawamura K, Kato S, Unemi F, Kimura Y (1990) Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells. Thromb Res 57:617-623 (Pubitemid 20110427)
49. Ikeda U, Ikeda M, Kano S, Kanbe T, Shimada K (1996) Effect of cilostazol, a cAMP phosphodiesterase inhibitor, on nitric oxide production by vascular smooth muscle cells. Eur J Pharmacol 314:197-202 (Pubitemid 26378904)
50. Ikenoya M, Doi T, Miura T, Sawanobori K, Nishio M, Hidaka H (2007) Investigation of binding proteins for anti-platelet agent K-134 by Drug-Western method. Biochem Biophys Res Commun 353:1111-1114 (Pubitemid 46084966)
51. Ikewaki K, Mochizuki K, Iwasaki M, Nishide R, Mochizuki S, Tada N (2002) Cilostazol, a potent phosphodiesterase type III inhibitor, selectively increases antiatherogenic high-density lipoprotein subclass LpA-I and improves postprandial lipemia in patients with type 2 diabetes mellitus. Metabolism 51:1348-1354 (Pubitemid 35174158)
52. Inada H, Shindo H, Tawata M, Onaya T (1999) Cilostazol, a cyclic AMP phosphodiesterase inhibitor, stimulates nitric oxide production and sodium potassium adenosine triphosphatase activity in SH-SY5Y human neuroblastoma cells. Life Sci 65:1413-1422 (Pubitemid 29425981)
53. Indolfi C, Di LE, Rapacciuolo A, Stingone AM, Stabile E, Leccia A, Torella D, Caputo R, Ciardiello F, Tortora G, Chiariello M (2000) 8-chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo. J Am Coll Cardiol 36:288-293 (Pubitemid 30466147)
54. Ishikawa M, Yamada Y, Hirose C, Tujino D, Hoshi K, Saitou N (1997) The effects of cilostazol on serum lipid metabolism and ASO in NIDDM with hypertriglyceridemia. Ther Res 18:198-204 (Pubitemid 27418236)
55. Ishiwata N, Noguchi K, Kawanishi M, Asakura Y, Hori M, Mitani A, Ito Y, Takahashi K, Nishiyama H, Shudo N, Takahashi S, Takahashi K, Tsuruzoe N, Nakaike S (2007) NT-702 (parogrelil hydrochloride, NM-702), a novel and potent phosphodiesterase inhibitor, improves reduced walking distance and lowered hindlimb plantar surface temperature in a rat experimental intermittent claudication model. Life Sci 81:970-978 (Pubitemid 47386005)
56. Ito H, Hashimoto A, Matsumoto Y, Yao H, Miyakoda G (2010) Cilostazol, a phosphodiesterase inhibitor, attenuates photothrombotic focal ischemic brain injury in hypertensive rats. J Cereb Blood Flow Metab 30:343-351
57. Iwama D, Miyamoto K, Miyahara S, Tamura H, Tsujikawa A, Yamashiro K, Kiryu J, Yoshimura N (2007) Neuroprotective effect of cilostazol against retinal ischemic damage via inhibition of leukocyte-endothelial cell interactions. J Thromb Haemost 5:818-825 (Pubitemid 46563583)
58. Jackson SP, Nesbitt WS, Westein E (2009) Dynamics of platelet thrombus formation. J Thromb Haemost 7(Suppl 1):17-20
59. Kambayashi SY, Liu Y (2007) Bench to bedside: multiple actions of PDE3 inhibitor cilostazol. In: Beavo JA, Francis SH, Houslay MD (eds) Cyclic nucleotide phosphodiesterases in health and disease. CRC Press, Boca Raton, FL, pp 627-648
60. Kambayashi J, Liu Y, Sun B, Shakur Y, Yoshitake M, Czerwiec F (2003) Cilostazol as a unique antithrombotic agent. Curr Pharm Des 9:2289-2308
61. Kasseckert SA, Schafer C, Kluger A, Gligorievski D, Tillmann J, Schluter KD, Noll T, Sauer H, Piper HM, Abdallah Y (2009) Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation. Cardiovasc Res 83:381-387
62. Kemp-Harper B, Schmidt HH (2009) cGMP in the vasculature. Handb Exp Pharmacol 191:447-467
63. Keravis SAP, Favot L, Lugnier C (2007) Role of PDEs in vascular health and disease: endothelial PDEs and angiogenesis. In: Beavo JA, Francis SH, Houslay MD (eds) Cyclic nucleotide phosphodiesterases in health and disease. CRC Press, Boca Raton, FL, pp 417-439
64. Kim KY, Shin HK, Choi JM, Hong KW (2002) Inhibition of lipopolysaccharide-induced apoptosis by cilostazol in human umbilical vein endothelial cells. J Pharmacol Exp Ther 300:709-715
65. Kimura Y, Tani T, Kanbe T, Watanabe K (1985) Effect of cilostazol on platelet aggregation and experimental thrombosis. Arzneimittelforschung 35:1144-1149 (Pubitemid 15030828)
66. Koga Y, Kihara Y, Okada M, Inoue Y, Tochizawa S, Toga K, Tachibana K, Kimura Y, Nishi T, Hidaka H (1998) 2(1H)-quinolinone derivatives as novel anti-arteriostenotic agents showing anti-thrombotic and anti-hyperplastic activities. Bioorg Med Chem Lett 8:1471-1476 (Pubitemid 28281407)
67. Lee JH, Kim KY, Lee YK, Park SY, Kim CD, Lee WS, Rhim BY, Hong KW (2004) Cilostazol prevents focal cerebral ischemic injury by enhancing casein kinase 2 phosphorylation and suppression of phosphatase and tensin homolog deleted from chromosome 10 phosphorylation in rats. J Pharmacol Exp Ther 308:896-903 (Pubitemid 38263963)
68. Lievre M, Morand S, Besse B, Fiessinger JN, Boissel JP (2000) Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: a double-blind, randomized, multicenter controlled trial. Beraprost et Claudication Intermittente (BERCI) Research Group. Circulation 102:426-431 (Pubitemid 30490681)
69. Liu Y, Fong M, Cone J, Wang S, Yoshitake M, Kambayashi J (2000) Inhibition of adenosine uptake and augmentation of ischemia-induced increase of interstitial adenosine by cilostazol, an agent to treat intermittent claudication. J Cardiovasc Pharmacol 36:351-360 (Pubitemid 30660466)
70. Liu Y, Shakur Y, Yoshitake M, Kambayashi JJ (2001) Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc Drug Rev 19:369-386 (Pubitemid 34260705)
71. Loscalzo J (2001) Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circ Res 88:756-762 (Pubitemid 32429970)
72. Madamanchi NR, Vendrov A, Runge MS (2005) Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25:29-38 (Pubitemid 40054251)
73. Manickavasagam S, Ye Y, Lin Y, Perez-Polo RJ, Huang MH, Lui CY, Hughes MG, McAdoo DJ, Uretsky BF, Birnbaum Y (2007) The cardioprotective effect of a statin and cilostazol combination: relationship to Akt and endothelial nitric oxide synthase activation. Cardiovasc Drugs Ther 21:321-330 (Pubitemid 47598922)
74. Maurice DH (2005) Cyclic nucleotide phosphodiesterase-mediated integration of cGMP and cAMP signaling in cells of the cardiovascular system. Front Biosci 10:1221-1228
75. Maurice DH, Palmer D, Tilley DG, Dunkerley HA, Netherton SJ, Raymond DR, Elbatarny HS, Jimmo SL (2003) Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system. Mol Pharmacol 64:533-546 (Pubitemid 37048555)
76. Mishima Y, Kuyama A, Ando M, Kibata M, Ishioka T (2000) Effects of cilostazol on serum lipoprotein concentrations and particle size of low-density lipoproteins in patients with dyslipidemic NIDDM. J Jpn Atheroscler Soc 27:17-22
77. Mizutani M, Okuda Y, Yamashita K (1996) Effect of cilostazol on the production of plateletderived growth factor in cultured human vascular endothelial cells. Biochem Mol Med 57:156-158 (Pubitemid 26142738)
78. Moher D, Pham B, Ausejo M, Saenz A, Hood S, Barber GG (2000) Pharmacological management of intermittent claudication: a meta-analysis of randomised trials. Drugs 59:1057-1070 (Pubitemid 30339130)
79. Mohler ER III, Beebe HG, Salles-Cuhna S, Zimet R, Zhang P, Heckman J, Forbes WP (2001) Effects of cilostazol on resting ankle pressures and exercise-induced ischemia in patients with intermittent claudication. Vasc Med 6:151-156 (Pubitemid 33138277)
80. Mohler ER III, Hiatt WR, Creager MA (2003a) Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation 108:1481-1486 (Pubitemid 37176455)
81. Mohler ER III, Hiatt WR, Olin JW, Wade M, Jeffs R, Hirsch AT (2003b) Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2 analogue: a doubleblinded, randomized, controlled trial. J Am Coll Cardiol 41:1679-1686 (Pubitemid 36584234)
82. Mondillo S, Ballo P, Barbati R, Guerrini F, Ammaturo T, Agricola E, Pastore M, Borrello F, Belcastro M, Picchi A, Nami R (2003) Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease. Am J Med 114:359-364 (Pubitemid 36513683)
83. Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L, Marini M, Orlando C, Vannelli GB, Aversa A, Natali A, Forti G, Giorgi M, Jannini EA, Ledda F, Maggi M (2004) Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology 145:2253-2263 (Pubitemid 38535054)
84. Mori D, Ishii H, Kojima C, Nitta N, Nakajima K, Yoshida M (2007) Cilostazol inhibits monocytic cell adhesion to vascular endothelium via upregulation of cAMP. J Atheroscler Thromb 14:213-218
85. Movsesian MA (2002) PDE3 cyclic nucleotide phosphodiesterases and the compartmentation of cyclic nucleotide-mediated signalling in cardiac myocytes. Basic Res Cardiol 97(Suppl 1): I83-I90
86. Movsesian MA, Kukreja RC (2011) Phosphodiesterase inhibition in heart failure. In: Francis SH, Conti M, Houslay MD (eds) Phosphodiesterases as drug targets. Springer, Heidelberg
87. Muller-Buhl U, Diehm C, Krais T, Zimmermann R, Morl H, Eckstein HH (1987) Clinical effects of intravenous iloprost in patients with intermittent claudication. Eur J Clin Pharmacol 33:127-131 (Pubitemid 17149223)
88. Nakamura T, Houchi H, Minami A, Sakamoto S, Tsuchiya K, Niwa Y, Minakuchi K, Nakaya Y (2001) Endothelium-dependent relaxation by cilostazol, a phosphodiesteras III inhibitor, on rat thoracic aorta. Life Sci 69:1709-1715 (Pubitemid 32785280)
89. Nakamura N, Hamazaki T, Johkaji H, Minami S, Yamazaki K, Satoh A, Sawazaki S, Urakaze M, Kobayashi M, Osawa H, Yamabe H, Okomura K (2003) Effects of cilostazol on serum lipid concentrations and plasma fatty acid composition in type 2 diabetic patients with peripheral vascular disease. Clin Exp Med 2:180-184 (Pubitemid 36313184)
90. Nesbitt WS, Westein E, Tovar-Lopez FJ, Tolouei E, Mitchell A, Fu J, Carberry J, Fouras A, Jackson SP (2009) A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat Med 15:665-673
91. Netherton SJ, Maurice DH (2005) Vascular endothelial cell cyclic nucleotide phosphodiesterases and regulated cell migration: implications in angiogenesis. Mol Pharmacol 67:263-272 (Pubitemid 40069987)
92. Nieswandt B, Watson SP (2003) Platelet-collagen interaction: is GPVI the central receptor? Blood 102:449-461 (Pubitemid 36841960)
93. Nishi T, Tabusa F, Tanaka T, Shimizu T, Nakagawa K (1985) Studies on 2-oxoquinoline derivatives as blood platelet aggregation inhibitors, IV. Synthesis and biological activity of the metabolites of 6-[4-(1-cyclohexyl-1H-5- tetrazolyl)butoxy]-2-oxo-1, 2, 3, 4-tetrahydroquinoline (OPC-13013). Chem Pharm Bull (Tokyo) 33:1140-1147 (Pubitemid 15104068)
94. Ohshima N, Sato M (1981) Effect of pentoxifylline on microvascular blood flow velocity. Angiology 32:752-763 (Pubitemid 12173650)
95. Oka RK, Szuba A, Giacomini JC, Cooke JP (2005) A pilot study of L-arginine supplementation on functional capacity in peripheral arterial disease. Vasc Med 10:265-274 (Pubitemid 43137276)
96. Omi H, Okayama N, Shimizu M, Fukutomi T, Nakamura A, Imaeda K, Okouchi M, ItohM (2004) Cilostazol inhibits high glucose-mediated endothelial-neutrophil adhesion by decreasing adhesion molecule expression via NO production. Microvasc Res 68:119-125 (Pubitemid 39093885)
97. Osinski MT, Schror K (2000) Inhibition of platelet-derived growth factor-induced mitogenesis by phosphodiesterase 3 inhibitors: role of protein kinase A in vascular smooth muscle cell mitogenesis. Biochem Pharmacol 60:381-387 (Pubitemid 30336635)
98. Page CP, Spina D (2011) PDE inhibitors in the treatment of inflammatory diseases. In: Francis SH, Conti M, Houslay MD (eds) Phosphodiesterases as drug targets. Springer, Heidelberg
99. Sanz MJ, Cortijo J, Taha MA, Cerda-Nicolas M, Schatton E, Burgbacher B, Klar J, Tenor H, Schudt C, Issekutz AC, Hatzelmann A, Morcillo EJ (2007) Roflumilast inhibits leukocyteendothelial cell interactions, expression of adhesion molecules and microvascular permeability. Br J Pharmacol 152:481-492 (Pubitemid 47585048)
100. Schafer A, Flierl U, Kobsar A, Eigenthaler M, Ertl G, Bauersachs J (2006) Soluble guanylyl cyclase activation with HMR1766 attenuates platelet activation in diabetic rats. Arterioscler Thromb Vasc Biol 26:2813-2818
101. Schindler U, Strobel H, Schonafinger K, Linz W, Lohn M, Martorana PA, Rutten H, Schindler PW, Busch AE, Sohn M, Topfer A, Pistorius A, Jannek C, Mulsch A (2006) Biochemistry and pharmacology of novel anthranilic acid derivatives activating heme-oxidized soluble guanylyl cyclase. Mol Pharmacol 69:1260-1268
102. Schmidt U, Han RO, DiSalvo TG, Guerrero JL, Gold HK, Zapol WM, Bloch KD, Semigran MJ (2001) Cessation of platelet-mediated cyclic canine coronary occlusion after thrombolysis by combining nitric oxide inhalation with phosphodiesterase-5 inhibition. J Am Coll Cardiol 37:1981-1988 (Pubitemid 32499990)
103. Schwarz UR, Walter U, Eigenthaler M (2001) Taming platelets with cyclic nucleotides. Biochem Pharmacol 62:1153-1161 (Pubitemid 33055619)
104. Snyder PB (1999) The adipocyte of cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE3B) as a target for lipolytic and thermogenic agents for the treatment of obesity. Emerg Ther Targets 3:587-599
105. Snyder PB, Esselstyn JM, Loughney K, Wolda SL, Florio VA (2005) The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis. J Lipid Res 46:494-503 (Pubitemid 43109786)
106. Stewart KJ, Hiatt WR, Regensteiner JG, Hirsch AT (2002) Exercise training for claudication. N Engl J Med 347:1941-1951
107. Sudo T, Tachibana K, Toga K, Tochizawa S, Inoue Y, Kimura Y, Hidaka H (2000) Potent effects of novel anti-platelet aggregatory cilostamide analogues on recombinant cyclic nucleotide phosphodiesterase isozyme activity. Biochem Pharmacol 59:347-356 (Pubitemid 30015963)
108. Sun B, Le SN, Lin S, Fong M, Guertin M, Liu Y, Tandon NN, Yoshitake M, Kambayashi J (2002) New mechanism of action for cilostazol: interplay between adenosine and cilostazol in inhibiting platelet activation. J Cardiovasc Pharmacol 40:577-585
109. Sun B, Li H, Shakur Y, Hensley J, Hockman S, Kambayashi J, Manganiello VC, Liu Y (2007) Role of phosphodiesterase type 3A and 3B in regulating platelet and cardiac function using subtype-selective knockout mice. Cell Signal 19:1765-1771 (Pubitemid 46935432)
110. Takayoshi T, Shinichi O, Ryuzo A, Ryuichi S, Norihiro S, Hisamichi S, Akira F (2001) Effect of cilostazol on lipid, uric acid and glucose metabolism in patients with impaired glucose tolerance or type 2 diabetes mellitus: a double-blind, placebo-controlled study. Clin Drug Investig 21:325-335
111. Tamai T, Shimada A, Maeda H, Takahashi S, Oida K, Nakai T, Miyabo S (1992) Reduction of low density lipoprotein by cilostazol in the non-insulin dependent diabetic patient. Jpn Pharmacol Ther 20:241-248 (Pubitemid 23024232)
112. Thompson WJ, Ashikaga T, Kelly JJ, Liu L, Zhu B, Vemavarapu L, Strada SJ (2002) Regulation of cyclic AMP in rat pulmonary microvascular endothelial cells by rolipram-sensitive cyclic AMP phosphodiesterase (PDE4). Biochem Pharmacol 63:797-807 (Pubitemid 34457713)
113. Thompson PE, Manganiello V, Degerman E (2007) Re-discovering PDE3 inhibitors-new opportunities for a long neglected target. Curr Top Med Chem 7:421-436 (Pubitemid 46358654)
114. Torii H, Kubota H, Ishihara H, Suzuki M (2007) Cilostazol inhibits the redistribution of the actin cytoskeleton and junctional proteins on the blood-brain barrier under hypoxia/reoxygenation. Pharmacol Res 55:104-110 (Pubitemid 46186035)
115. Traupe T, Ortmann J, Munter K, Barton M (2003) Endothelial therapy of atherosclerosis and its risk factors. Curr Vasc Pharmacol 1:111-121
116. Tsai EJ, Kass DA (2009) Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther 122:216-238
117. van Hattum ES, Algra A, Lawson JA, Eikelboom BC, Moll FL, Tangelder MJD (2009) Bleeding increases the risk of ischemic events in patients with peripheral arterial disease. Circulation 120:1569-1576
118. Wakida K, Morimoto N, ShimazawaM, Hozumi I, Nagase H, Inuzuka T, Hara H (2006) Cilostazol reduces ischemic brain damage partly by inducing metallothionein-1 and -2. Brain Res 1116:187-193 (Pubitemid 44485011)
119. Wang S, Cone J, Fong M, Yoshitake M, Kambayashi J, Liu Y (2001) Interplay between inhibition of adenosine uptake and phosphodiesterase type 3 on cardiac function by cilostazol, an agent to treat intermittent claudication. J Cardiovasc Pharmacol 38:775-783 (Pubitemid 32983284)
120. Wang YX, Fitch R, Li W, Werner M, Halks-Miller M, Lillis B, Vergona R, Post J, Sullivan ME, Verhallen PF (2002) Reduction of cardiac functional reserve and elevation of aortic stiffness in hyperlipidemic Yucatan minipigs with systemic and coronary atherosclerosis. Vascul Pharmacol 39:69-76 (Pubitemid 36398247)
121. Wang T, Elam MB, Forbes WP, Zhong J, Nakajima K (2003) Reduction of remnant lipoprotein cholesterol concentrations by cilostazol in patients with intermittent claudication. Atherosclerosis 171:337-342 (Pubitemid 37492883)
122. Watanabe N, Ishikawa Y, Kitagawa Y, Ozaki M, Takeshita S, Namura H, Kurimoto Y, Yamada S, Yokoyama M (1996) Effects of cilostazol on the lipid metabolism in patients with hypertriglyceridemia. Jpn Pharmacol Ther 24:127-132 (Pubitemid 26052969)
123. Wilson AM, Harada R, Nair N, Balasubramanian N, Cooke JP (2007) L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation 116:188-195 (Pubitemid 47057525)
124. Wilson LS, Elbatarny HS, Crawley SW, Bennett BM, Maurice DH (2008) Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMPmediated regulation of platelet functions. Proc Natl Acad Sci USA 105:13650-13655
125. Yang Y, Luo J, Kazumura K, Takeuchi K, Inui N, Hayashi H, Ohashi K, Watanabe H (2006) Cilostazol suppresses adhesion of human neutrophils to HUVECs stimulated by FMLP and its mechanisms. Life Sci 79:629-636 (Pubitemid 43927974)
126. Yoshikawa T, Mitani K, Kotosai K, Nozako M, Miyakoda G, Yabuuchi Y (2008) Antiatherogenic effects of cilostazol and probucol alone, and in combination in low density lipoprotein receptor-deficient mice fed with a high fat diet. Horm Metab Res 40:473-478
127. Yuzawa I, Yamada M, Fujii K (2008) An oral administration of cilostazol before focal ischemia reduces the infarct volume with delayed cerebral blood flow increase in rats. J Stroke Cerebrovasc Dis 17:281-286
128. Zaccolo M, Movsesian MA (2007) cAMP and cGMP signaling cross-talk: role of phosphodiesterases and implications for cardiac pathophysiology. Circ Res 100:1569-1578 (Pubitemid 46897260)
129. ZhangW, Colman RW(2007) Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A. Blood 110:1475-1482 (Pubitemid 47443962)
130. Zhao H, Guan Q, Smith CJ, Quilley J (2008) Increased phosphodiesterase 3A/4B expression after angioplasty and the effect on VASP phosphorylation. Eur J Pharmacol 590:29-35
131. Zhu B, Strada S, Stevens T (2005) Cyclic GMP-specific phosphodiesterase 5 regulates growth and apoptosis in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 289:L196-L206 (Pubitemid 41008901)