Remodeling of calcium handling in human heart failure

Advances in Experimental Medicine and Biology

Volumn 740, Issue , 2012, Pages 1145-1174

  Lou, Qing ^a   Janardhan, Ajit ^b   Efimov, Igor R ^a  

^a WASHINGTON UNIVERSITY IN ST LOUIS   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Calcium; Clinical treatment; Heart failure; Human; Remodeling

Indexed keywords

AMLODIPINE; ANGIOTENSIN II; BETA ADRENERGIC RECEPTOR; CALCIUM CHANNEL BLOCKING AGENT; G PROTEIN COUPLED RECEPTOR KINASE; PHOSPHOLAMBAN; PROTEIN KINASE C ALPHA; REACTIVE OXYGEN METABOLITE; RYANODINE RECEPTOR; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SODIUM CALCIUM EXCHANGE PROTEIN;

ARTICLE; BETA ADRENERGIC STIMULATION; CALCIUM BINDING; CALCIUM CELL LEVEL; CALCIUM HOMEOSTASIS; CALCIUM SIGNALING; CALCIUM TRANSPORT; CARDIOMYOPATHY; DISEASE ASSOCIATION; DRUG INDICATION; ENZYME ACTIVITY; HEART ARRHYTHMIA; HEART DEPOLARIZATION; HEART FAILURE; HEART FUNCTION; HEART MUSCLE ISCHEMIA; HEART MUSCLE POTENTIAL; HORMONE INHIBITION; HUMAN; MECHANICAL STRESS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; SYMPATHETIC TONE;

ARRHYTHMIAS, CARDIAC; CALCIUM; CALCIUM SIGNALING; HEART FAILURE; HUMANS; MYOCARDIUM; RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL; SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES;

EID: 84859902405     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-94-007-2888-2_52     Document Type: Article

References (186)

1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C (2010) Heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation 121(7):e46
2. Bui AL, Horwich TB, Fonarow GC (2011) Epidemiology and risk profile of heart failure. Nat Rev Cardiol 8(1):30-41
3. Bers DM (2001) Excitation-contraction coupling and cardiac contractile force. Springer, The Netherlands
4. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4(7):517-529
5. Morgan JP (1991) Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N Engl J Med 325(9):625-632
6. Hasenfuss G, Pieske B, Holubarsch C, Alpert NR, Just H (1993) Excitation-contraction coupling and contractile protein function in failing and nonfailing human myocardium. Adv Exp Med Biol 346:91-100
7. Katz AM (1990) Cardiomyopathy of overload. A major determinant of prognosis in congestive heart failure. N Engl J Med 322(2):100-110
8. Bohm M, Reiger B, Schwinger RH, Erdmann E (1994) cAMP concentrations, cAMP dependent protein kinase activity, and phospholamban in non-failing and failing myocardium. Cardiovasc Res 28(11):1713-1719
9. Kirchhefer U, Schmitz W, Scholz H, Neumann J (1999) Activity of cAMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human hearts. Cardiovasc Res 42(1):254-261
10. Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR (2000) PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 101(4):365-376
11. Lehnart SE, Wehrens XH, Reiken S, Warrier S, Belevych AE, Harvey RD, Richter W, Jin SL, Conti M, Marks AR (2005) Phosphodiesterase 4D Deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell 123(1):25-35
12. Maier LS, Bers DM (2007) Role of Ca2+/calmodulin-dependent protein kinase (CaMK) in excitation-contraction coupling in the heart. Cardiovasc Res 73(4):631-640
13. Wehrens XH, Lehnart SE, Reiken SR, Marks AR (2004) Ca2+/calmodulin- dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor. Circ Res 94(6):e61-e70
14. Hain J, Onoue H, Mayrleitner M, Fleischer S, Schindler H (1995) Phosphorylation modulates the function of the calcium release channel of sarcoplasmic reticulum from cardiac muscle. J Biol Chem 270(5):2074-2081
15. Currie S, Loughrey CM, Craig MA, Smith GL (2004) Calcium/calmodulin- dependent protein kinase IIdelta associates with the ryanodine receptor complex and regulates channel function in rabbit heart. Biochem J 377(Pt 2):357-366
16. Sossalla S, Fluschnik N, Schotola H, Ort KR, Neef S, Schulte T, Wittkopper K, Renner A, Schmitto JD, Gummert J, El-Armouche A, Hasenfuss G, Maier LS (2010) Inhibition of elevated Ca2+/calmodulin-dependent protein kinase II improves contractility in human failing myocardium. Circ Res 107(9):1150-1161
17. Hambleton M, Hahn H, Pleger ST, Kuhn MC, Klevitsky R, Carr AN, Kimball TF, Hewett TE, Dorn GW 2nd, Koch WJ, Molkentin JD (2006) Pharmacological-and gene therapy-based inhibition of protein kinase Calpha/beta enhances cardiac contractility and attenuates heart failure. Circulation 114(6):574-582
18. Yano M, Ikeda Y, Matsuzaki M (2005) Altered intracellular Ca2+ handling in heart failure. J Clin Invest 115(3):556-564
19. Braz JC, Gregory K, Pathak A, Zhao W, Sahin B, Klevitsky R, Kimball TF, Lorenz JN, Nairn AC, Liggett SB, Bodi I, Wang S, Schwartz A, Lakatta EG, DePaoli-Roach AA, Robbins J, Hewett TE, Bibb JA, Westfall MV, Kranias EG, Molkentin JD (2004) PKC-alpha regulates cardiac contractility and propensity toward heart failure. Nat Med 10(3):248-254
20. Bowling N, Walsh RA, Song G, Estridge T, Sandusky GE, Fouts RL, Mintze K, Pickard T, Roden R, Bristow MR, Sabbah HN, Mizrahi JL, Gromo G, King GL, Vlahos CJ (1999) Increased protein kinase C activity and expression of Ca2+ -sensitive isoforms in the failing human heart. Circulation 99(3):384-391
21. Wang J, Liu X, Sentex E, Takeda N, Dhalla NS (2003) Increased expression of protein kinase C isoforms in heart failure due to myocardial infarction. Am J Physiol Heart Circ Physiol 284(6):H2277-H2287
22. Simonis G, Briem SK, Schoen SP, Bock M, Marquetant R, Strasser RH (2007) Protein kinase C in the human heart: differential regulation of the isoforms in aortic stenosis or dilated cardiomyopathy. Mol Cell Biochem 305(1-2):103-111
23. Yue DT, Marban E, Wier WG (1986) Relationship between force and intracellular [Ca2+] in tetanized mammalian heart muscle. J Gen Physiol 87(2):223-242
24. Gwathmey JK, Copelas L, MacKinnon R, Schoen FJ, Feldman MD, Grossman W, Morgan JP (1987) Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 61(1):70-76
25. Gwathmey JK, Slawsky MT, Hajjar RJ, Briggs GM, Morgan JP (1990) Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium. J Clin Invest 85(5):1599-1613
26. Beuckelmann DJ, Nabauer M, Erdmann E (1991) Characteristics of calcium-current in isolated human ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol 23(8):929-937
27. Gwathmey JK, Warren SE, Briggs GM, Copelas L, Feldman MD, Phillips PJ, Callahan M Jr, Schoen FJ, Grossman W, Morgan JP (1991) Diastolic dysfunction in hypertrophic cardiomyopathy. Effect on active force generation during systole. J Clin Invest 87(3):1023-1031
28. Beuckelmann DJ, Nabauer M, Erdmann E (1992) Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation 85(3):1046-1055
29. Pieske B, Kretschmann B, Meyer M, Holubarsch C, Weirich J, Posival H, Minami K, Just H, Hasenfuss G (1995) Alterations in intracellular calcium handling associated with the inverse force-frequency relation in human dilated cardiomyopathy. Circulation 92(5):1169-1178
30. Piacentino V 3rd, Weber CR, Chen X, Weisser-Thomas J, Margulies KB, Bers DM, Houser SR (2003) Cellular basis of abnormal calcium transients of failing human ventricular myocytes. Circ Res 92(6):651-658
31. Lou Q, Fedorov VV, Glukhov AV, Moazami N, Fast VG, Efi mov IR (2011) Transmural heterogeneity and remodeling of ventricular excitation-contraction coupling in human heart failure. Circulation 123:1881-1890
32. Vahl CF, Bonz A, Timek T, Hagl S (1994) Intracellular calcium transient of working human myocardium of seven patients transplanted for congestive heart failure. Circ Res 74(5):952-958
33. Allen DG, Blinks JR (1978) Calcium transients in aequorin-injected frog cardiac muscle. Nature 273(5663):509-513
34. Blinks JR, Wier WG, Hess P, Prendergast FG (1982) Measurement of Ca2+ concentrations in living cells. Prog Biophys Mol Biol 40(1-2):1-114
35. Kubo H, Margulies KB, Piacentino V 3rd, Gaughan JP, Houser SR (2001) Patients with endstage congestive heart failure treated with beta-adrenergic receptor antagonists have improved ventricular myocyte calcium regulatory protein abundance. Circulation 104(9):1012-1018
36. Hasenfuss G, Mulieri LA, Leavitt BJ, Allen PD, Haeberle JR, Alpert NR (1992) Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy. Circ Res 70(6):1225-1232
37. Gomez AM, Valdivia HH, Cheng H, Lederer MR, Santana LF, Cannell MB, McCune SA, Altschuld RA, Lederer WJ (1997) Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure. Science 276(5313):800-806
38. Lindner M, Erdmann E, Beuckelmann DJ (1998) Calcium content of the sarcoplasmic reticulum in isolated ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol 30(4):743-749
39. Pieske B, Maier LS, Bers DM, Hasenfuss G (1999) Ca2+ handling and sarcoplasmic reticulum Ca2+ content in isolated failing and nonfailing human myocardium. Circ Res 85(1):38-46
40. Hobai IA, O'Rourke B (2001) Decreased sarcoplasmic reticulum calcium content is responsible for defective excitation-contraction coupling in canine heart failure. Circulation 103(11):1577-1584
41. Dipla K, Mattiello JA, Margulies KB, Jeevanandam V, Houser SR (1999) The sarcoplasmic reticulum and the Na+/Ca2+ exchanger both contribute to the Ca2+ transient of failing human ventricular myocytes. Circ Res 84(4):435-444
42. Pieske B, Maier LS, Piacentino V 3rd, Weisser J, Hasenfuss G, Houser S (2002) Rate dependence of [Na+ ]i and contractility in nonfailing and failing human myocardium. Circulation 106(4):447-453
43. Hasenfuss G, Pieske B (2002) Calcium cycling in congestive heart failure. J Mol Cell Cardiol 34(8):951-969
44. Feldman MD, Alderman JD, Aroesty JM, Royal HD, Ferguson JJ, Owen RM, Grossman W, McKay RG (1988) Depression of systolic and diastolic myocardial reserve during atrial pacing tachycardia in patients with dilated cardiomyopathy. J Clin Invest 82(5):1661-1669
45. Mulieri LA, Hasenfuss G, Leavitt B, Allen PD, Alpert NR (1992) Altered myocardial forcefrequency relation in human heart failure. Circulation 85(5):1743-1750
46. Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, Holubarsch C, Posival H, Just H, Drexler H (1994) Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circ Res 75(3):434-442
47. Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L (2010) Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebocontrolled study. Lancet 376(9744):875-885
48. Orn S, Dickstein K (2002) How do heart failure patients die? Eur Heart J Suppl 4(suppl D) D59
49. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH (2005) Amiodarone or an implantable cardioverter-defi brillator for congestive heart failure. N Engl J Med 352(3):225-237
50. Tomaselli GF, Marban E (1999) Electrophysiological remodeling in hypertrophy and heart failure. Cardiovasc Res 42(2):270-283
51. Pogwizd SM, Schlotthauer K, Li L, Yuan W, Bers DM (2001) Arrhythmogenesis and contractile dysfunction in heart failure: roles of sodium-calcium exchange, inward rectifi er potassium current, and residual beta-adrenergic responsiveness. Circ Res 88(11):1159-1167
52. Belevych AE, Terentyev D, Terentyeva R, Nishijima Y, Sridhar A, Hamlin RL, Carnes CA, Gyorke S (2011) The relationship between arrhythmogenesis and impaired contractility in heart failure: role of altered ryanodine receptor function. Cardiovasc Res 90(3):493-502
53. Tomaselli GF, Beuckelmann DJ, Calkins HG, Berger RD, Kessler PD, Lawrence JH, Kass D, Feldman AM, Marban E (1994) Sudden cardiac death in heart failure. The role of abnormal repolarization. Circulation 90(5):2534-2539
54. Weiss JN, Garfi nkel A, Karagueuzian HS, Chen PS, Qu Z (2010) Early afterdepolarizations and cardiac arrhythmias. Heart Rhythm 7(12):1891-1899
55. Pogwizd SM, Bers DM (2004) Cellular basis of triggered arrhythmias in heart failure. Trends Cardiovasc Med 14(2):61-66
56. Pogwizd SM, McKenzie JP, Cain ME (1998) Mechanisms underlying spontaneous and induced ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy. Circulation 98(22):2404-2414
57. Vermeulen JT, McGuire MA, Opthof T, Coronel R, de Bakker JM, Klopping C, Janse MJ (1994) Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. Cardiovasc Res 28(10):1547-1554
58. Pruvot EJ, Katra RP, Rosenbaum DS, Laurita KR (2004) Role of calcium cycling versus restitution in the mechanism of repolarization alternans. Circ Res 94(8):1083-1090
59. Wilson LD, Jeyaraj D, Wan X, Hoeker GS, Said TH, Gittinger M, Laurita KR, Rosenbaum DS (2009) Heart failure enhances susceptibility to arrhythmogenic cardiac alternans. Heart Rhythm 6(2):251-259
60. Klingenheben T, Zabel M, D'Agostino RB, Cohen RJ, Hohnloser SH (2000) Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure. Lancet 356(9230):651-652
61. Pastore JM, Girouard SD, Laurita KR, Akar FG, Rosenbaum DS (1999) Mechanism linking T-wave alternans to the genesis of cardiac fibrillation. Circulation 99(10):1385-1394
62. Cutler MJ, Wan X, Laurita KR, Hajjar RJ, Rosenbaum DS (2009) Targeted SERCA2a gene expression identifi es molecular mechanism and therapeutic target for arrhythmogenic cardiac alternans. Circ Arrhythm Electrophysiol 2(6):686-694
63. Mewes T, Ravens U (1994) L-type calcium currents of human myocytes from ventricle of non-failing and failing hearts and from atrium. J Mol Cell Cardiol 26(10):1307-1320
64. Sipido KR, Stankovicova T, Flameng W, Vanhaecke J, Verdonck F (1998) Frequency dependence of Ca2+ release from the sarcoplasmic reticulum in human ventricular myocytes from end-stage heart failure. Cardiovasc Res 37(2):478-488
65. Lindner M, Brandt MC, Sauer H, Hescheler J, Bohle T, Beuckelmann DJ (2002) Calcium sparks in human ventricular cardiomyocytes from patients with terminal heart failure. Cell Calcium 31(4):175-182
66. Crossman DJ, Ruygrok PR, Soeller C, Cannell MB (2011) Changes in the organization of excitation-contraction coupling structures in failing human heart. PLoS One 6(3):e17901
67. Lyon AR, MacLeod KT, Zhang Y, Garcia E, Kanda GK, Lab MJ, Korchev YE, Harding SE, Gorelik J (2009) Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart. Proc Natl Acad Sci USA 106(16):6854-6859
68. Ohler A, Weisser-Thomas J, Piacentino V, Houser SR, Tomaselli GF, O'Rourke B (2009) Two-photon laser scanning microscopy of the transverse-axial tubule system in ventricular cardiomyocytes from failing and non-failing human hearts. Cardiol Res Pract 2009:802373
69. Song LS, Sobie EA, McCulle S, Lederer WJ, Balke CW, Cheng H (2006) Orphaned ryanodine receptors in the failing heart. Proc Natl Acad Sci USA 103(11):4305-4310
70. Louch WE, Bito V, Heinzel FR, Macianskiene R, Vanhaecke J, Flameng W, Mubagwa K, Sipido KR (2004) Reduced synchrony of Ca2+ release with loss of T-tubules-a comparison to Ca2+ release in human failing cardiomyocytes. Cardiovasc Res 62(1):63-73
71. Wasserstrom JA, Sharma R, Kapur S, Kelly JE, Kadish AH, Balke CW, Aistrup GL (2009) Multiple defects in intracellular calcium cycling in whole failing rat heart. Circ Heart Fail 2(3):223-232
72. Jantunen E, Collan Y (1989) Transmural differences in ischaemic heart disease: a quantitative histologic study. Appl Pathol 7(3):179-187
73. Figueredo VM, Brandes R, Weiner MW, Massie BM, Camacho SA (1993) Endocardial versus epicardial differences of intracellular free calcium under normal and ischemic conditions in perfused rat hearts. Circ Res 72(5):1082-1090
74. Burashnikov A, Antzelevitch C (2003) Reinduction of atrial fibrillation immediately after termination of the arrhythmia is mediated by late phase 3 early afterdepolarization-induced triggered activity. Circulation 107(18):2355-2360
75. Sobie EA, Guatimosim S, Song LS, Lederer WJ (2003) The challenge of molecular medicine: complexity versus Occam's razor. J Clin Invest 111(6):801-803
76. Jaski BE, Jessup ML, Mancini DM, Cappola TP, Pauly DF, Greenberg B, Borow K, Dittrich H, Zsebo KM, Hajjar RJ (2009) Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID Trial), a fi rst-in-human phase 1/2 clinical trial. J Card Fail 15(3):171-181
77. Kubalova Z, Terentyev D, Viatchenko-Karpinski S, Nishijima Y, Gyorke I, Terentyeva R, da Cunha DN, Sridhar A, Feldman DS, Hamlin RL, Carnes CA, Gyorke S (2005) Abnormal intrastore calcium signaling in chronic heart failure. Proc Natl Acad Sci USA 102(39):14104-14109
78. Jiang MT, Lokuta AJ, Farrell EF, Wolff MR, Haworth RA, Valdivia HH (2002) Abnormal Ca2+ release, but normal ryanodine receptors, in canine and human heart failure. Circ Res 91(11):1015-1022
79. Li Y, Kranias EG, Mignery GA, Bers DM (2002) Protein kinase A phosphorylation of the ryanodine receptor does not affect calcium sparks in mouse ventricular myocytes. Circ Res 90(3):309-316
80. Ai X, Curran JW, Shannon TR, Bers DM, Pogwizd SM (2005) Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure. Circ Res 97(12):1314-1322
81. Kushnir A, Shan J, Betzenhauser MJ, Reiken S, Marks AR (2010) Role of CaMKIIdelta phosphorylation of the cardiac ryanodine receptor in the force frequency relationship and heart failure. Proc Natl Acad Sci USA 107(22):10274-10279
82. De Koninck P, Schulman H (1998) Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations. Science 279(5348):227-230
83. Zhao W, Uehara Y, Chu G, Song Q, Qian J, Young K, Kranias EG (2004) Threonine-17 phosphorylation of phospholamban: a key determinant of frequency-dependent increase of cardiac contractility. J Mol Cell Cardiol 37(2):607-612
84. Holmberg SR, Williams AJ (1989) Single channel recordings from human cardiac sarcoplasmic reticulum. Circ Res 65(5):1445-1449
85. Schmidt U, Hajjar RJ, Kim CS, Lebeche D, Doye AA, Gwathmey JK (1999) Human heart failure: cAMP stimulation of SR Ca(2+)-ATPase activity and phosphorylation level of phospholamban. Am J Physiol 277(2 Pt 2):H474-H480
86. Schwinger RH, Bohm M, Schmidt U, Karczewski P, Bavendiek U, Flesch M, Krause EG, Erdmann E (1995) Unchanged protein levels of SERCA II and phospholamban but reduced Ca2+ uptake and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation 92(11):3220-3228
87. del Monte F, Harding SE, Schmidt U, Matsui T, Kang ZB, Dec GW, Gwathmey JK, Rosenzweig A, Hajjar RJ (1999) Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a. Circulation 100(23):2308-2311
88. del Monte F, Harding SE, Dec GW, Gwathmey JK, Hajjar RJ (2002) Targeting phospholamban by gene transfer in human heart failure. Circulation 105(8):904-907
89. Frank KF, Bolck B, Brixius K, Kranias EG, Schwinger RH (2002) Modulation of SERCA: implications for the failing human heart. Basic Res Cardiol 97(Suppl 1):I72-I78
90. Schwinger RH, Munch G, Bolck B, Karczewski P, Krause EG, Erdmann E (1999) Reduced Ca(2+)-sensitivity of SERCA 2a in failing human myocardium due to reduced serin-16 phospholamban phosphorylation. J Mol Cell Cardiol 31(3):479-491
91. Dash R, Frank KF, Carr AN, Moravec CS, Kranias EG (2001) Gender influences on sarcoplasmic reticulum Ca2+ -handling in failing human myocardium. J Mol Cell Cardiol 33(7): 1345-1353
92. Munch G, Bolck B, Karczewski P, Schwinger RH (2002) Evidence for calcineurin-mediated regulation of SERCA 2a activity in human myocardium. J Mol Cell Cardiol 34(3):321-334
93. Mishra S, Gupta RC, Tiwari N, Sharov VG, Sabbah HN (2002) Molecular mechanisms of reduced sarcoplasmic reticulum Ca(2+) uptake in human failing left ventricular myocardium. J Heart Lung Transplant 21(3):366-373
94. Minamisawa S, Hoshijima M, Chu G, Ward CA, Frank K, Gu Y, Martone ME, Wang Y, Ross J Jr, Kranias EG, Giles WR, Chien KR (1999) Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 99(3):313-322
95. Liu Q, Chen X, Macdonnell SM, Kranias EG, Lorenz JN, Leitges M, Houser SR, Molkentin JD (2009) Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach. Circ Res 105(2):194-200
96. Weber CR, Piacentino V 3rd, Houser SR, Bers DM (2003) Dynamic regulation of sodium/calcium exchange function in human heart failure. Circulation 108(18):2224-2229
97. Ventura-Clapier R, Garnier A, Veksler V (2004) Energy metabolism in heart failure. J Physiol 555(Pt 1):1-13
98. Bers DM (2008) Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol 70:23-49
99. De Sousa E, Veksler V, Minajeva A, Kaasik A, Mateo P, Mayoux E, Hoerter J, Bigard X, Serrurier B, Ventura-Clapier R (1999) Subcellular creatine kinase alterations. Implications in heart failure. Circ Res 85(1):68-76
100. Xu KY, Zweier JL, Becker LC (1997) Hydroxyl radical inhibits sarcoplasmic reticulum Ca(2+)-ATPase function by direct attack on the ATP binding site. Circ Res 80(1):76-81
101. Hasenfuss G, Maier LS, Hermann HP, Luers C, Hunlich M, Zeitz O, Janssen PM, Pieske B (2002) Infl uence of pyruvate on contractile performance and Ca(2+) cycling in isolated failing human myocardium. Circulation 105(2):194-199
102. Reiken S, Wehrens XH, Vest JA, Barbone A, Klotz S, Mancini D, Burkhoff D, Marks AR (2003) Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure. Circulation 107(19):2459-2466
103. Chaudhary KW, Rossman EI, Piacentino V 3rd, Kenessey A, Weber C, Gaughan JP, Ojamaa K, Klein I, Bers DM, Houser SR, Margulies KB (2004) Altered myocardial Ca2+ cycling after left ventricular assist device support in the failing human heart. J Am Coll Cardiol 44(4):837-845
104. Vanderheyden M, Mullens W, Delrue L, Goethals M, de Bruyne B, Wijns W, Geelen P, Verstreken S, Wellens F, Bartunek J (2008) Myocardial gene expression in heart failure patients treated with cardiac resynchronization therapy responders versus nonresponders. J Am Coll Cardiol 51(2):129-136
105. del Monte F, Williams E, Lebeche D, Schmidt U, Rosenzweig A, Gwathmey JK, Lewandowski ED, Hajjar RJ (2001) Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase in a rat model of heart failure. Circulation 104(12):1424-1429
106. Rockman HA, Koch WJ, Lefkowitz RJ (2002) Seven-transmembrane-spanning receptors and heart function. Nature 415(6868):206-212
107. Cambronero F, Marin F, Roldan V, Hernandez-Romero D, Valdes M, Lip GY (2009) Biomarkers of pathophysiology in hypertrophic cardiomyopathy: implications for clinical management and prognosis. Eur Heart J 30(2):139-151
108. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW (2009) 2009 Focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines developed in collaboration with the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 53(15):e1-e90
109. Wehrens XH, Lehnart SE, Huang F, Vest JA, Reiken SR, Mohler PJ, Sun J, Guatimosim S, Song LS, Rosemblit N, D'Armiento JM, Napolitano C, Memmi M, Priori SG, Lederer WJ, Marks AR (2003) FKBP12.6 Deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 113(7):829-840
110. DeSantiago J, Maier LS, Bers DM (2002) Frequency-dependent acceleration of relaxation in the heart depends on CaMKII, but not phospholamban. J Mol Cell Cardiol 34(8):975-984
111. Sugden PH, Bogoyevitch MA (1995) Intracellular signalling through protein kinases in the heart. Cardiovasc Res 30(4):478-492
112. Kluger J, Cody RJ, Laragh JH (1982) The contributions of sympathetic tone and the reninangiotensin system to severe chronic congestive heart failure: response to specific inhibitors (prazosin and captopril). Am J Cardiol 49(7):1667-1674
113. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T (1984) Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Eng J Med 311(13):819-823
114. Ungerer M, Bohm M, Elce JS, Erdmann E, Lohse MJ (1993) Altered expression of betaadrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart. Circulation 87(2):454-463
115. Daaka Y, Luttrell LM, Lefkowitz RJ (1997) Switching of the coupling of the beta2-adrenergic receptor to different G proteins by protein kinase A. Nature 390(6655):88-91
116. Bristow MR, Minobe WA, Raynolds MV, Port JD, Rasmussen R, Ray PE, Feldman AM (1993) Reduced beta 1 receptor messenger RNA abundance in the failing human heart. J Clin Invest 92(6):2737-2745
117. Wei SK, Ruknudin A, Hanlon SU, McCurley JM, Schulze DH, Haigney MC (2003) Protein kinase A hyperphosphorylation increases basal current but decreases beta-adrenergic responsiveness of the sarcolemmal Na+ -Ca2+ exchanger in failing pig myocytes. Circ Res 92(8): 897-903
118. Beta-Blocker Evaluation of Survival Trial Investigators (2001) A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Eng J Med 344(22):1659-1667
119. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH (1996) The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 334(21):1349-1355
120. MERIT-HFTrial (1999) Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353(9169):2001-2007
121. CIBIS-IITrial (1999) The Cardiac Insuffi ciency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 353(9146):9-13
122. Yancy CW (2005) Comprehensive treatment of heart failure: state-of-the-art medical therapy. Rev Cardiovasc Med 6(Suppl 2):S43-S57
123. Bristow MR (2000) beta-adrenergic receptor blockade in chronic heart failure. Circulation 101(5):558-569
124. Lowes BD, Gilbert EM, Abraham WT, Minobe WA, Larrabee P, Ferguson D, Wolfel EE, Lindenfeld J, Tsvetkova T, Robertson AD, Quaife RA, Bristow MR (2002) Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents. N Engl J Med 346(18):1357-1365
125. Reiken S, Gaburjakova M, Gaburjakova J, He Kl KL, Prieto A, Becker E, Yi Gh GH, Wang J, Burkhoff D, Marks AR (2001) beta-adrenergic receptor blockers restore cardiac calcium release channel (ryanodine receptor) structure and function in heart failure. Circulation 104(23):2843-2848
126. Reiken S, Gaburjakova M, Guatimosim S, Gomez AM, D'Armiento J, Burkhoff D, Wang J, Vassort G, Lederer WJ, Marks AR (2003) Protein kinase A phosphorylation of the cardiac calcium release channel (ryanodine receptor) in normal and failing hearts. Role of phosphatases and response to isoproterenol. J Biol Chem 278(1):444-453
127. Yano M, Ono K, Ohkusa T, Suetsugu M, Kohno M, Hisaoka T, Kobayashi S, Hisamatsu Y, Yamamoto T, Noguchi N, Takasawa S, Okamoto H, Matsuzaki M (2000) Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure. Circulation 102(17):2131-2136
128. Doi M, Yano M, Kobayashi S, Kohno M, Tokuhisa T, Okuda S, Suetsugu M, Hisamatsu Y, Ohkusa T, Matsuzaki M (2002) Propranolol prevents the development of heart failure by restoring FKBP12.6-mediated stabilization of ryanodine receptor. Circulation 105(11): 1374-1379
129. George I, Sabbah HN, Xu K, Wang N, Wang J (2011) {Beta}-adrenergic receptor blockade reduces endoplasmic reticulum stress and normalizes calcium handling in a coronary embolization model of heart failure in canines. Cardiovasc Res 91(3):447-455
130. Beuckelmann DJ, Nabauer M, Kruger C, Erdmann E (1995) Altered diastolic [Ca2+] i handling in human ventricular myocytes from patients with terminal heart failure. Am Heart J 129(4):684-689
131. Pass JM, Gao J, Jones WK, Wead WB, Wu X, Zhang J, Baines CP, Bolli R, Zheng YT, Joshua IG, Ping P (2001) Enhanced PKC beta II translocation and PKC beta II-RACK1 interactions in PKC epsilon-induced heart failure: a role for RACK1. Am J Physiol Heart Circ Physiol 281(6):H2500-H2510
132. Silberman GA, Fan TH, Liu H, Jiao Z, Xiao HD, Lovelock JD, Boulden BM, Widder J, Fredd S, Bernstein KE, Wolska BM, Dikalov S, Harrison DG, Dudley SC Jr (2010) Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation 121(4):519-528
133. Mende U, Kagen A, Cohen A, Aramburu J, Schoen FJ, Neer EJ (1998) Transient cardiac expression of constitutively active Galphaq leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways. Proc Natl Acad Sci USA 95(23): 13893-13898
134. Taigen T, De Windt LJ, Lim HW, Molkentin JD (2000) Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy. Proc Natl Acad Sci USA 97(3): 1196-1201
135. Thomas WG, Brandenburger Y, Autelitano DJ, Pham T, Qian H, Hannan RD (2002) Adenoviraldirected expression of the type 1A angiotensin receptor promotes cardiomyocyte hypertrophy via transactivation of the epidermal growth factor receptor. Circ Res 90(2):135-142
136. Wilkins BJ, Molkentin JD (2004) Calcium-calcineurin signaling in the regulation of cardiac hypertrophy. Biochem Biophys Res Commun 322(4):1178-1191
137. Sussman MA, Lim HW, Gude N, Taigen T, Olson EN, Robbins J, Colbert MC, Gualberto A, Wieczorek DF, Molkentin JD (1998) Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science 281(5383):1690-1693
138. Maack C, Kartes T, Kilter H, Schafers HJ, Nickenig G, Bohm M, Laufs U (2003) Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation 108(13):1567-1574
139. Giordano FJ (2005) Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 115(3):500-508
140. Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh K, Colucci WS (2002) Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol 34(4):379-388
141. Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK (2002) Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators. Circ Res 91(5):406-413
142. Rathore N, John S, Kale M, Bhatnagar D (1998) Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res 38(4):297-303
143. Thollon C, Iliou JP, Cambarrat C, Robin F, Vilaine JP (1995) Nature of the cardiomyocyte injury induced by lipid hydroperoxides. Cardiovasc Res 30(5):648-655
144. Suematsu N, Tsutsui H, Wen J, Kang D, Ikeuchi M, Ide T, Hayashidani S, Shiomi T, Kubota T, Hamasaki N, Takeshita A (2003) Oxidative stress mediates tumor necrosis factor-alphainduced mitochondrial DNA damage and dysfunction in cardiac myocytes. Circulation 107(10):1418-1423
145. Nishida M, Maruyama Y, Tanaka R, Kontani K, Nagao T, Kurose H (2000) G alpha(i) and G alpha(o) are target proteins of reactive oxygen species. Nature 408(6811):492-495
146. Guerra L, Cerbai E, Gessi S, Borea PA, Mugelli A (1996) The effect of oxygen free radicals on calcium current and dihydropyridine binding sites in guinea-pig ventricular myocytes. Br J Pharmacol 118(5):1278-1284
147. Kaplan P, Babusikova E, Lehotsky J, Dobrota D (2003) Free radical-induced protein modifi -cation and inhibition of Ca2+ -ATPase of cardiac sarcoplasmic reticulum. Mol Cell Biochem 248(1-2):41-47
148. Goldhaber JI (1996) Free radicals enhance Na+/Ca2+ exchange in ventricular myocytes. Am J Physiol 271(3 Pt 2):H823-H833
149. Okuda S, Yano M, Doi M, Oda T, Tokuhisa T, Kohno M, Kobayashi S, Yamamoto T, Ohkusa T, Matsuzaki M (2004) Valsartan restores sarcoplasmic reticulum function with no appreciable effect on resting cardiac function in pacing-induced heart failure. Circulation 109(7):911-919
150. Agostoni PG, De Cesare N, Doria E, Polese A, Tamborini G, Guazzi MD (1986) Afterload reduction: a comparison of captopril and nifedipine in dilated cardiomyopathy. Br Heart J 55(4):391-399
151. Tan LB, Murray RG, Littler WA (1987) Felodipine in patients with chronic heart failure: discrepant haemodynamic and clinical effects. Br Heart J 58(2):122-128
152. Elkayam U, Amin J, Mehra A, Vasquez J, Weber L, Rahimtoola SH (1990) A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and
153. Cohn JN, Ziesche S, Smith R, Anand I, Dunkman WB, Loeb H, Cintron G, Boden W, Baruch L, Rochin P, Loss L (1997) Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group. Circulation 96(3):856-863
154. Elkayam U, Parikh K, Torkan B, Weber L, Cohen JL, Rahimtoola SH (1985) Effect of diltiazem on renal clearance and serum concentration of digoxin in patients with cardiac disease. Am J Cardiol 55(11):1393-1395
155. Barjon JN, Rouleau JL, Bichet D, Juneau C, De Champlain J (1987) Chronic renal and neurohumoral effects of the calcium entry blocker nisoldipine in patients with congestive heart failure. J Am Coll Cardiol 9(3):622-630
156. Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S (1991) Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group. Circulation 83(1):52-60
157. Littler WA, Sheridan DJ (1995) Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group. Br Heart J 73(5):428-433
158. Mohindra SK, Udeani GO (1989) Long-acting verapamil and heart failure. JAMA 261(7):994
159. Levine TB, Bernink PJ, Caspi A, Elkayam U, Geltman EM, Greenberg B, McKenna WJ, Ghali JK, Giles TD, Marmor A, Reisin LH, Ammon S, Lindberg E (2000) Effect of mibefradil, a T-type calcium channel blocker, on morbidity and mortality in moderate to severe congestive heart failure: the MACH-1 study. Mortality assessment in congestive heart failure trial. Circulation 101(7):758-764
160. Mullins ME, Horowitz BZ, Linden DH, Smith GW, Norton RL, Stump J (1998) Life-threatening interaction of mibefradil and beta-blockers with dihydropyridine calcium channel blockers. JAMA 280(2):157-158
161. Benatar D, Hall V, Reddy S, Gheorghiade M (1998) Clinical and neurohormonal effects of nicardipine hydrochloride in patients with severe chronic heart failure receiving angiotensinconverting enzyme inhibitor therapy. Am J Ther 5(1):25-32
162. Packer M, O'Connor CM, Ghali JK, Pressler ML, Carson PE, Belkin RN, Miller AB, Neuberg GW, Frid D, Wertheimer JH, Cropp AB, DeMets DL (1996) Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective randomized amlodipine survival evaluation study group. N Eng J Med 335(15):1107-1114
163. Freedman NJ, Liggett SB, Drachman DE, Pei G, Caron MG, Lefkowitz RJ (1995) Phosphorylation and desensitization of the human beta 1-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase. J Biol Chem 270(30):17953-17961
164. Harding VB, Jones LR, Lefkowitz RJ, Koch WJ, Rockman HA (2001) Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure. Proc Natl Acad Sci USA 98(10):5809-5814
165. Rockman HA, Chien KR, Choi DJ, Iaccarino G, Hunter JJ, Ross J Jr, Lefkowitz RJ, Koch WJ (1998) Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc Natl Acad Sci USA 95(12):7000-7005
166. Marx SO, Reiken S, Hisamatsu Y, Gaburjakova M, Gaburjakova J, Yang YM, Rosemblit N, Marks AR (2001) Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers. J Cell Biol 153(4):699-708
167. Most P, Koch WJ (2003) Sealing the leak, healing the heart. Nat Med 9(8):993-994
168. Wehrens XH, Lehnart SE, Reiken SR, Deng SX, Vest JA, Cervantes D, Coromilas J, Landry DW, Marks AR (2004) Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2. Science 304(5668):292-296
169. Yano M, Kobayashi S, Kohno M, Doi M, Tokuhisa T, Okuda S, Suetsugu M, Hisaoka T, Obayashi M, Ohkusa T, Matsuzaki M (2003) FKBP12.6-mediated stabilization of calciumrelease channel (ryanodine receptor) as a novel therapeutic strategy against heart failure. Circulation 107(3):477-484
170. Zhang R, Khoo MS, Wu Y, Yang Y, Grueter CE, Ni G, Price EE Jr, Thiel W, Guatimosim S, Song LS, Madu EC, Shah AN, Vishnivetskaya TA, Atkinson JB, Gurevich VV, Salama G, Lederer WJ, Colbran RJ, Anderson ME (2005) Calmodulin kinase II inhibition protects against structural heart disease. Nat Med 11(4):409-417
171. Limas CJ, Olivari MT, Goldenberg IF, Levine TB, Benditt DG, Simon A (1987) Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardiovasc Res 21(8):601-605
172. Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE (2003) Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science 299(5611):1410-1413
173. Huang B, Wang S, Qin D, Boutjdir M, El-Sherif N (1999) Diminished basal phosphorylation level of phospholamban in the postinfarction remodeled rat ventricle: role of beta-adrenergic pathway, G(i) protein, phosphodiesterase, and phosphatases. Circ Res 85(9):848-855
174. Hoshijima M, Ikeda Y, Iwanaga Y, Minamisawa S, Date MO, Gu Y, Iwatate M, Li M, Wang L, Wilson JM, Wang Y, Ross J Jr, Chien KR (2002) Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med 8(8):864-871
175. Iwanaga Y, Hoshijima M, Gu Y, Iwatate M, Dieterle T, Ikeda Y, Date MO, Chrast J, Matsuzaki M, Peterson KL, Chien KR, Ross J Jr (2004) Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J Clin Invest 113(5):727-736
176. Kaye DM, Preovolos A, Marshall T, Byrne M, Hoshijima M, Hajjar R, Mariani JA, Pepe S, Chien KR, Power JM (2007) Percutaneous cardiac recirculation- mediated gene transfer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals. J Am Coll Cardiol 50(3):253-260
177. Yamada M, Ikeda Y, Yano M, Yoshimura K, Nishino S, Aoyama H, Wang L, Aoki H, Matsuzaki M (2006) Inhibition of protein phosphatase 1 by inhibitor-2 gene delivery ameliorates heart failure progression in genetic cardiomyopathy. FASEB J 20(8):1197-1199
178. Dawson J, Walters M (2006) Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease? Br J Clin Pharmacol 62(6):633-644
179. Spector T (1988) Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol 37(2):349-352
180. Cappola TP, Kass DA, Nelson GS, Berger RD, Rosas GO, Kobeissi ZA, Marban E, Hare JM (2001) Allopurinol improves myocardial effi ciency in patients with idiopathic dilated cardiomyopathy. Circulation 104(20):2407-2411
181. Freudenberger RS, Schwarz RP Jr, Brown J, Moore A, Mann D, Givertz MM, Colucci WS, Hare JM (2004) Rationale, design and organisation of an efficacy and safety study of oxypurinol added to standard therapy in patients with NYHA class III-IV congestive heart failure. Expert Opin Investig Drugs 13(11):1509-1516
182. Hare JM, Mangal B, Brown J, Fisher C Jr, Freudenberger R, Colucci WS, Mann DL, Liu P, Givertz MM, Schwarz RP (2008) Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J Am Coll Cardiol 51(24):2301-2309
183. Brillantes AM, Allen P, Takahashi T, Izumo S, Marks AR (1992) Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with endstage heart failure caused by ischemic versus dilated cardiomyopathy. Circ Res 71(1):18-26
184. Sen L, Cui G, Fonarow GC, Laks H (2000) Differences in mechanisms of SR dysfunction in ischemic vs. idiopathic dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 279(2):H709-H718
185. Houser SR (2001) Reduced abundance of transverse tubules and L-type calcium channels: another cause of defective contractility in failing ventricular myocytes. Cardiovasc Res 49(2):253-256
186. Efi mov IR, Fedorov VV, Glukhov A, Lou Q, Ambrosi C, Janks D, Hucker WJ, Kurian T, Schuessler RB, Moazami N (2010) Multiscale imaging of the human heart: building the foundation for human systems physiology and translational medicine. Conf Proc IEEE Eng Med Biol Soc 2010:5177-5180