Cyclosporin A and cardioprotection: From investigative tool to therapeutic agent

British Journal of Pharmacology

Volumn 165, Issue 5, 2012, Pages 1235-1245

  Hausenloy, D J ^a   Boston Griffiths, E A ^a   Yellon, D M ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

cardioprotection; cyclosporin A; ischaemia; myocardial infarction; reperfusion

Indexed keywords

CREATINE KINASE; CYCLOPHILIN; CYCLOSPORIN A; CYCLOSPORIN A [4 N METHYLISOLEUCINE]; CYCLOSPORIN B; DEBIO 0125; INTERLEUKIN 2; INTERLEUKIN 3; INTERLEUKIN 4; LACTATE DEHYDROGENASE; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; PROTON PUMP INHIBITOR; TACROLIMUS; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ACUTE HEART INFARCTION; BINDING AFFINITY; BINDING SITE; CALCIUM METABOLISM; CELL PROLIFERATION; DRUG ACTIVITY; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; ENZYME ACTIVITY; GRAFT REJECTION; HEART INFARCTION; HEART INFARCTION SIZE; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; ISCHEMIC HEART DISEASE; LIPOPHILICITY; LIVER ISCHEMIA; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; REPERFUSION INJURY; REVIEW; SOMATIC CELL; T LYMPHOCYTE;

ANIMALS; CARDIOTONIC AGENTS; CYCLOSPORINE; HUMANS; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MYOCARDIAL ISCHEMIA; MYOCARDIUM;

EID: 84857098116     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01700.x     Document Type: Review

References (82)

1. Al Nasser I, Crompton M, (1986a). The entrapment of the Ca2+ indicator arsenazo III in the matrix space of rat liver mitochondria by permeabilization and resealing. Na+-dependent and -independent effluxes of Ca2+ in arsenazo III-loaded mitochondria. Biochem J 239: 31-40.
2. Al Nasser I, Crompton M, (1986b). The reversible Ca2+-induced permeabilization of rat liver mitochondria. Biochem J 239: 19-29.
3. Altschuld RA, Hohl CM, Castillo LC, Garleb AA, Starling RC, Brierley GP, (1992). Cyclosporin inhibits mitochondrial calcium efflux in isolated adult rat ventricular cardiomyocytes. Am J Physiol 262: H1699-H1704.
4. Argaud L, Gateau-Roesch O, Chalabreysse L, Gomez L, Loufouat J, Thivolet-Bejui F, et al,. (2004). Preconditioning delays Ca2+-induced mitochondrial permeability transition. Cardiovasc Res 61: 115-122.
5. Argaud L, Gateau-Roesch O, Muntean D, Chalabreysse L, Loufouat J, Robert D, et al,. (2005a). Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury. J Mol Cell Cardiol 38: 367-374.
6. Argaud L, Gateau-Roesch O, Raisky O, Loufouat J, Robert D, Ovize M, (2005b). Postconditioning inhibits mitochondrial permeability transition. Circulation 111: 194-197.
7. Arteaga D, Odor A, Lopez RM, Contreras G, Pichardo J, Garcia E, et al,. (1992). Impairment by cyclosporin A of reperfusion-induced arrhythmias. Life Sci 51: 1127-1134.
8. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, et al,. (2005). Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434: 658-662.
9. Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD, (2007). Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9: 550-555.
10. Basso E, Fante L, Fowlkes J, Petronilli V, Forte MA, Bernardi P, (2005). Properties of the permeability transition pore in mitochondria devoid of cyclophilin D. J Biol Chem 280: 18558-18561.
11. Borel JF, Kis ZL, (1991). The discovery and development of cyclosporine (Sandimmune). Transplant Proc 23: 1867-1874.
12. Braunwald E, Kloner RA, (1985). Myocardial reperfusion: a double-edged sword? J Clin Invest 76: 1713-1719.
13. Broekemeier KM, Dempsey ME, Pfeiffer DR, (1989). Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. J Biol Chem 264: 7826-7830.
14. Clarke SJ, McStay GP, Halestrap AP, (2002). Sanglifehrin A acts as a potent inhibitor of the mitochondrial permeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A. J Biol Chem 277: 34793-34799.
15. Cour M, Loufouat J, Paillard M, Augeul L, Goudable J, Ovize M, et al,. (2011). Inhibition of mitochondrial permeability transition to prevent the post-cardiac arrest syndrome: a pre-clinical study. Eur Heart J 32: 226-235.
16. Crompton M, (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem J 341 (Pt 2): 233-249.
17. Crompton M, Costi A, Hayat L, (1987). Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria. Biochem J 245: 915-918.
18. Crompton M, Ellinger H, Costi A, (1988). Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem J 255: 357-360.
19. Di Lisa F, Menabo R, Canton M, Barile M, Bernardi P, (2001). Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD+ and is a causative event in the death of myocytes in postischemic reperfusion of the heart. J Biol Chem 276: 2571-2575.
20. Di Lisa F, Carpi A, Giorgio V, Bernardi P, (2011). The mitochondrial permeability transition pore and cyclophilin D in cardioprotection. Biochim Biophys Acta 1813: 1316-1322.
21. Elrod JW, Wong R, Mishra S, Vagnozzi RJ, Sakthievel B, Goonasekera SA, et al,. (2010). Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice. J Clin Invest 120: 3680-3687.
22. Ferdinandy P, Schulz R, Baxter GF, (2007). Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol Rev 59: 418-458.
23. Fischer G, Wittmann-Liebold B, Lang K, Kiefhaber T, Schmid FX, (1989). Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins. Nature 337: 476-478.
24. Fournier N, Ducet G, Crevat A, (1987). Action of cyclosporine on mitochondrial calcium fluxes. J Bioenerg Biomembr 19: 297-303.
25. Ghosh S, Standen NB, Galinianes M, (2001). Failure to precondition pathological human myocardium. J Am Coll Cardiol 37: 711-718.
26. Gomez L, Thibault H, Gharib A, Dumont JM, Vuagniaux G, Scalfaro P, et al,. (2007). Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice. Am J Physiol Heart Circ Physiol 293: H1654-H1661.
27. Griffiths EJ, Halestrap AP, (1991). Further evidence that cyclosporin A protects mitochondria from calcium overload by inhibiting a matrix peptidyl-prolyl cis-trans isomerase. Implications for the immunosuppressive and toxic effects of cyclosporin. Biochem J 274 (Pt 2): 611-614.
28. Griffiths EJ, Halestrap AP, (1993). Protection by cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts. J Mol Cell Cardiol 25: 1461-1469.
29. Griffiths EJ, Halestrap AP, (1995). Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem J 307 (Pt 1): 93-98.
30. Gunter TE, Pfeiffer DR, (1990). Mechanisms by which mitochondria transport calcium. Am J Physiol 258: C755-C786.
31. Halestrap AP, (2009). Mitochondria and reperfusion injury of the heart-a holey death but not beyond salvation. J Bioenerg Biomembr 41: 113-121.
32. Halestrap AP, Davidson AM, (1990). Inhibition of Ca2(+)-induced large-amplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenine nucleotide translocase. Biochem J 268: 153-160.
33. Handschumacher RE, Harding MW, Rice J, Drugge RJ, Speicher DW, (1984). Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science 226: 544-547.
34. Hausenloy DJ, Yellon DM, (2003). The mitochondrial permeability transition pore: its fundamental role in mediating cell death during ischaemia and reperfusion. J Mol Cell Cardiol 35: 339-341.
35. Hausenloy DJ, Yellon DM, (2008). Time to take myocardial reperfusion injury seriously. N Engl J Med 359: 518-520.
36. Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM, (2002). Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res 55: 534-543.
37. Hausenloy DJ, Duchen MR, Yellon DM, (2003). Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury. Cardiovasc Res 60: 617-625.
38. Hausenloy DJ, Yellon DM, Mani-Babu S, Duchen MR, (2004). Preconditioning protects by inhibiting the mitochondrial permeability transition. Am J Physiol Heart Circ Physiol 287: H841-H849.
39. Hayashi T, Nagasue N, Kohno H, Chang YC, Nakamura T, (1988). Beneficial effect of cyclosporine pretreatment in preventing ischemic damage to the liver in dogs. Transplantation 46: 923-924.
40. Huhn R, Heinen A, Hollmann MW, Schlack W, Preckel B, Weber NC, (2010). Cyclosporine A administered during reperfusion fails to restore cardioprotection in prediabetic Zucker obese rats in vivo. Nutr Metab Cardiovasc Dis 20: 706-712.
41. Javadov SA, Clarke S, Das M, Griffiths EJ, Lim KH, Halestrap AP, (2003). Ischaemic preconditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart. J Physiol 549: 513-524.
42. Jung K, Pergande M, (1985). Influence of cyclosporin A on the respiration of isolated rat kidney mitochondria. FEBS Lett 183: 167-169.
43. Karlsson LO, Zhou AX, Larsson E, Astrom-Olsson K, Mansson C, Akyurek LM, et al,. (2010). Cyclosporine does not reduce myocardial infarct size in a porcine ischemia-reperfusion model. J Cardiovasc Pharmacol Ther 15: 182-189.
44. Kawano K, Kim YI, Kaketani K, Kobayashi M, (1989). The beneficial effect of cyclosporine on liver ischemia in rats. Transplantation 48: 759-764.
45. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, et al,. (2004). The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427: 461-465.
46. Leung CH, Wang L, Fu YY, Yuen W, Caldarone CA, (2011). Transient mitochondrial permeability transition pore opening after neonatal cardioplegic arrest. J Thorac Cardiovasc Surg 141: 975-982.
47. Lim SY, Davidson SM, Hausenloy DJ, Yellon DM, (2007). Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore. Cardiovasc Res 75: 530-535.
48. Lim SY, Hausenloy DJ, Arjun S, Price AN, Davidson SM, Lythgoe MF, et al,. (2010). Mitochondrial cyclophilin-D as a potential therapeutic target for post-myocardial infarction heart failure. J Cell Mol Med. doi:10.1111/j.1582- 4934.2010.01235.x [Epub ahead of print].
49. Liu J, Farmer JD Jr, Lane WS, Friedman J, Weissman I, Schreiber SL, (1991). Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66: 807-815.
50. Malouitre S, Dube H, Selwood D, Crompton M, (2010). Mitochondrial targeting of cyclosporin A enables selective inhibition of cyclophilin-D and enhanced cytoprotection after glucose and oxygen deprivation. Biochem J 425: 137-148.
51. Matsumoto S, Friberg H, Ferrand-Drake M, Wieloch T, (1999). Blockade of the mitochondrial permeability transition pore diminishes infarct size in the rat after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab 19: 736-741.
52. Matsumoto-Ida M, Akao M, Takeda T, Kato M, Kita T, (2006). Real-time 2-photon imaging of mitochondrial function in perfused rat hearts subjected to ischemia/reperfusion. Circulation 114: 1497-1503.
53. Mewton N, Croisille P, Gahide G, Rioufol G, Bonnefoy E, Sanchez I, et al,. (2010). Effect of cyclosporine on left ventricular remodeling after reperfused myocardial infarction. J Am Coll Cardiol 55: 1200-1205.
54. Mihatsch MJ, Olivieri W, Marbet U, Thiel G, Harder F, Zollinger HU, (1981). Giant mitochondria in renal tubular cells and cyclosporin A. Lancet 1: 1162-1163.
55. Murata M, Akao M, O'Rourke B, Marban E, (2001). Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection. Circ Res 89: 891-898.
56. Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, et al,. (2005). Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434: 652-658.
57. Nakayama H, Chen X, Baines CP, Klevitsky R, Zhang X, Zhang H, et al,. (2007). Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest 117: 2431-2444.
58. Nazareth W, Yafei N, Crompton M, (1991). Inhibition of anoxia-induced injury in heart myocytes by cyclosporin A. J Mol Cell Cardiol 23: 1351-1354.
59. Niemann CU, Saeed M, Akbari H, Jacobsen W, Benet LZ, Christians U, et al,. (2002). Close association between the reduction in myocardial energy metabolism and infarct size: dose-response assessment of cyclosporine. J Pharmacol Exp Ther 302: 1123-1128.
60. Oie E, Bjornerheim R, Clausen OP, Attramadal H, (2000). Cyclosporin A inhibits cardiac hypertrophy and enhances cardiac dysfunction during postinfarction failure in rats. Am J Physiol Heart Circ Physiol 278: H2115-H2123.
61. Oka N, Wang L, Mi W, Caldarone CA, (2008). Inhibition of mitochondrial remodeling by cyclosporine A preserves myocardial performance in a neonatal rabbit model of cardioplegic arrest. J Thorac Cardiovasc Surg 135: 585-593.
62. Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, et al,. (2008). Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 359: 473-481.
63. Piper HM, Garcia-Dorado D, Ovize M, (1998). A fresh look at reperfusion injury. Cardiovasc Res 38: 291-300.
64. Schaller S, Paradis S, Ngoh GA, Assaly R, Buisson B, Drouot C, et al,. (2010). TRO40303, a new cardioprotective compound, inhibits mitochondrial permeability transition. J Pharmacol Exp Ther 333: 696-706.
65. Schinzel AC, Takeuchi O, Huang Z, Fisher JK, Zhou Z, Rubens J, et al,. (2005). Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc Natl Acad Sci U S A 102: 12005-12010.
66. Schneider A, Ad N, Izhar U, Khaliulin I, Borman JB, Schwalb H, (2003). Protection of myocardium by cyclosporin A and insulin: in vitro simulated ischemia study in human myocardium. Ann Thorac Surg 76: 1240-1245.
67. Schreiber SL, Crabtree GR, (1992). The mechanism of action of cyclosporin A and FK506. Immunol Today 13: 136-142.
68. Shanmuganathan S, Hausenloy DJ, Duchen MR, Yellon DM, (2005). Mitochondrial permeability transition pore as a target for cardioprotection in the human heart. Am J Physiol Heart Circ Physiol 289: H237-H242.
69. Shiga Y, Onodera H, Matsuo Y, Kogure K, (1992). Cyclosporin A protects against ischemia-reperfusion injury in the brain. Brain Res 595: 145-148.
70. Skyschally A, Schulz R, Heusch G, (2010). Cyclosporine A at reperfusion reduces infarct size in pigs. Cardiovasc Drugs Ther 24: 85-87.
71. Squadrito F, Altavilla D, Squadrito G, Saitta A, Campo GM, Arlotta M, et al,. (1999). Cyclosporin-A reduces leukocyte accumulation and protects against myocardial ischaemia reperfusion injury in rats. Eur J Pharmacol 364: 159-168.
72. Sumpio BE, Baue AE, Chaudry IH, (1987). Alleviation of cyclosporine nephrotoxicity with verapamil and ATP-MgCl2. Mitochondrial respiratory and calcium studies. Ann Surg 206: 655-660.
73. Tanveer A, Virji S, Andreeva L, Totty NF, Hsuan JJ, Ward JM, et al,. (1996). Involvement of cyclophilin D in the activation of a mitochondrial pore by Ca2+ and oxidant stress. Eur J Biochem 238: 166-172.
74. Tropschug M, Nicholson DW, Hartl FU, Kohler H, Pfanner N, Wachter E, et al,. (1988). Cyclosporin A-binding protein (cyclophilin) of Neurospora crassa. One gene codes for both the cytosolic and mitochondrial forms. J Biol Chem 263: 14433-14440.
75. Tsang A, Hausenloy DJ, Mocanu MM, Carr RD, Yellon DM, (2005). Preconditioning the diabetic heart: the importance of akt phosphorylation. Diabetes 54: 2360-2364.
76. Van Buren CT, Flechner SM, Kerman RH, Vaughn W, Kahan BD, (1984). Cyclosporine improves outcome in high-risk cadaveric renal allograft recipients. Transplant Proc 16: 1162-1166.
77. Verani R, (1983). Giant mitochondria in renal tubular cells and cyclosporin. Lancet 2: 285-286.
78. Wei AC, Liu T, Cortassa S, Winslow RL, O'Rourke B, (2011). Mitochondrial Ca(2+) influx and efflux rates in guinea pig cardiac mitochondria: low and high affinity effects of cyclosporine A. Biochim Biophys Acta 1813: 1373-1381.
79. Weinbrenner C, Liu GS, Downey JM, Cohen MV, (1998). Cyclosporine A limits myocardial infarct size even when administered after onset of ischemia. Cardiovasc Res 38: 678-684.
80. Xie JR, Yu LN, (2007). Cardioprotective effects of cyclosporine A in an in vivo model of myocardial ischemia and reperfusion. Acta Anaesthesiol Scand 51: 909-913.
81. Yang CW, Ahn HJ, Han HJ, Kim WY, Li C, Shin MJ, et al,. (2001). Pharmacological preconditioning with low-dose cyclosporine or FK506 reduces subsequent ischemia/reperfusion injury in rat kidney. Transplantation 72: 1753-1759.
82. Yellon DM, Hausenloy DJ, (2007). Myocardial reperfusion injury. N Engl J Med 357: 1121-1135.