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Circulation Research. 1993;72:463-469

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Circulation Research, Vol 72, 463-469, Copyright © 1993 by American Heart Association

ARTICLES

Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium

M Arai, NR Alpert, DH MacLennan, P Barton and M Periasamy
Department of Physiology and Biophysics, University of Vermont College of Medicine, Burlington.

Recent studies have shown that intracellular Ca2+ handling is abnormal in the myocardium of patients with end-stage heart failure. Muscles from the failing hearts showed a prolonged Ca2+ transient and a diminished capacity to restore a low resting Ca2+ level during diastole. Accordingly, we examined whether this defect in Ca2+ transport function is due to alterations in sarcoplasmic reticulum gene expression. We determined the messenger RNA (mRNA) levels of sarcoplasmic reticulum Ca2+ transport proteins in failing human hearts from 17 cardiac transplant recipients with a diagnosis of dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The expression levels of each mRNA were compared with each other and then correlated with that of atrial natriuretic factor (ANF) mRNA in the failing ventricle. The mRNA levels for the calcium release channel (ryanodine receptor, RYR2), Ca2+ uptake pump (Ca(2+)-ATPase, SERCA2 isoform), and phospholamban differed significantly between heart samples but showed an inverse relation with that of ventricular ANF mRNA. In contrast, calsequestrin mRNA levels remained unchanged in these failing hearts. In addition, beta-myosin and alpha-cardiac actin mRNA levels also showed an inverse relation with ANF mRNA levels. These changes were observed in both right and left ventricles of hearts with congestive heart failure due to dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The results are consistent with the hypothesis that abnormal calcium handling in the sarcoplasmic reticulum of failing hearts is due to the altered expression of the genes encoding sarcoplasmic reticulum proteins.


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V. J. Owen, P. B. J. Burton, M. C. Michel, O. Zolk, M. Bohm, J. R. Pepper, P. J. R. Barton, M. H. Yacoub, and S. E. Harding
Myocardial Dysfunction in Donor Hearts : A Possible Etiology
Circulation, May 18, 1999; 99(19): 2565 - 2570.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
L. Hittinger, B. Ghaleh, J. Chen, J. G. Edwards, R. K. Kudej, M. Iwase, S.-J. Kim, S. F. Vatner, and D. E. Vatner
Reduced Subendocardial Ryanodine Receptors and Consequent Effects on Cardiac Function in Conscious Dogs With Left Ventricular Hypertrophy
Circ. Res., May 14, 1999; 84(9): 999 - 1006.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
G. F. Tomaselli and E. Marban
Electrophysiological remodeling in hypertrophy and heart failure
Cardiovasc Res, May 1, 1999; 42(2): 270 - 283.
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 Circ. Res.Home page
B. Hoch, R. Meyer, R. Hetzer, E.-G. Krause, and P. Karczewski
Identification and Expression of {delta}-Isoforms of the Multifunctional Ca2+/Calmodulin-Dependent Protein Kinase in Failing and Nonfailing Human Myocardium
Circ. Res., April 2, 1999; 84(6): 713 - 721.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
B. O'Rourke, D. A. Kass, G. F. Tomaselli, S. Kaab, R. Tunin, and E. Marban
Mechanisms of Altered Excitation-Contraction Coupling in Canine Tachycardia-Induced Heart Failure, I : Experimental Studies
Circ. Res., March 19, 1999; 84(5): 562 - 570.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
R. L. Winslow, J. Rice, S. Jafri, E. Marban, and B. O'Rourke
Mechanisms of Altered Excitation-Contraction Coupling in Canine Tachycardia-Induced Heart Failure, II : Model Studies
Circ. Res., March 19, 1999; 84(5): 571 - 586.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
T. Yeh Jr, A. S. Wechsler, L. J. Graham, K. E. Loesser, D. A. Sica, L. Wolfe, and E. R. Jakoi
Acute Brain Death Alters Left Ventricular Myocardial Gene Expression
J. Thorac. Cardiovasc. Surg., February 1, 1999; 117(2): 365 - 374.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Periasamy, T. D. Reed, L. H. Liu, Y. Ji, E. Loukianov, R. J. Paul, M. L. Nieman, T. Riddle, J. J. Duffy, T. Doetschman, et al.
Impaired Cardiac Performance in Heterozygous Mice with a Null Mutation in the Sarco(endo)plasmic Reticulum Ca2+-ATPase Isoform 2 (SERCA2) Gene
J. Biol. Chem., January 22, 1999; 274(4): 2556 - 2562.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
D. L. Baker, K. Hashimoto, I. L. Grupp, Y. Ji, T. Reed, E. Loukianov, G. Grupp, A. Bhagwhat, B. Hoit, R. Walsh, et al.
Targeted Overexpression of the Sarcoplasmic Reticulum Ca2+-ATPase Increases Cardiac Contractility in Transgenic Mouse Hearts
Circ. Res., December 14, 1998; 83(12): 1205 - 1214.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
M. Anger, A.-M. Lompre, O. Vallot, F. Marotte, L. Rappaport, and J.-L. S. MD
Cellular Distribution of Ca2+ Pumps and Ca2+ Release Channels in Rat Cardiac Hypertrophy Induced by Aortic Stenosis
Circulation, December 1, 1998; 98(22): 2477 - 2486.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
E. Loukianov, Y. Ji, I. L. Grupp, D. L. Kirkpatrick, D. L. Baker, T. Loukianova, G. Grupp, J. Lytton, R. A. Walsh, and M. Periasamy
Enhanced Myocardial Contractility and Increased Ca2+ Transport Function in Transgenic Hearts Expressing the Fast-Twitch Skeletal Muscle Sarcoplasmic Reticulum Ca2+-ATPase
Circ. Res., November 2, 1998; 83(9): 889 - 897.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y. Sato, D. G. Ferguson, H. Sako, G. W. Dorn II, V. J. Kadambi, A. Yatani, B. D. Hoit, R. A. Walsh, and E. G. Kranias
Cardiac-specific Overexpression of Mouse Cardiac Calsequestrin Is Associated with Depressed Cardiovascular Function and Hypertrophy in Transgenic Mice
J. Biol. Chem., October 23, 1998; 273(43): 28470 - 28477.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
H. K. B. SIMMERMAN and L. R. JONES
Phospholamban: Protein Structure, Mechanism of Action, and Role in Cardiac Function
Physiol Rev, October 1, 1998; 78(4): 921 - 947.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
A. Yao, Z. Su, A. Nonaka, I. Zubair, K. W. Spitzer, J. H. B. Bridge, G. Muelheims, J. Ross Jr., and W. H. Barry
Abnormal myocyte Ca2+ homeostasis in rabbits with pacing-induced heart failure
Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1441 - H1448.
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 J Am Coll CardiolHome page
B. S. Cain, D. R. Meldrum, K. S. Joo, J.-F. Wang, X. Meng, J. C. Cleveland Jr., A. Banerjee, and A. H. Harken
Human SERCA2a levels correlate inversely with age in senescent human myocardium
J. Am. Coll. Cardiol., August 1, 1998; 32(2): 458 - 467.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
K. Igarashi-Saito, H. Tsutsui, S. Yamamoto, M. Takahashi, S. Kinugawa, H. Tagawa, M. Usui, M. Yamamoto, K. Egashira, and A. Takeshita
Role of SR Ca2+-ATPase in contractile dysfunction of myocytes in tachycardia-induced heart failure
Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H31 - H40.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
O. Zolk, M. Flesch, G. Nickenig, P. Schnabel, and M. Bohm
Alteration of intracellular Ca2+-handling and receptor regulation in hypertensive cardiac hypertrophy: insights from Ren2-transgenic rats
Cardiovasc Res, July 1, 1998; 39(1): 242 - 256.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
W. H. Barry
Load-Dependent Myocyte Dysfunction
Circulation, June 16, 1998; 97(23): 2297 - 2298.
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 CirculationHome page
K. Dipla, J. A. Mattiello, V. Jeevanandam, S. R. Houser, and K. B. Margulies
Myocyte Recovery After Mechanical Circulatory Support in Humans With End-Stage Heart Failure
Circulation, June 16, 1998; 97(23): 2316 - 2322.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
I. Gombosova, P. Boknik, U. Kirchhefer, J. Knapp, H. Luss, F. U. Muller, T. Muller, U. Vahlensieck, W. Schmitz, G. S. Bodor, et al.
Postnatal changes in contractile time parameters, calcium regulatory proteins, and phosphatases
Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H2123 - H2132.
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 Cardiovasc ResHome page
D.A Eisner, A.W Trafford, M.E Dnaz, C.L Overend, and S.C O'Neill
The control of Ca release from the cardiac sarcoplasmic reticulum: regulation versus autoregulation
Cardiovasc Res, June 1, 1998; 38(3): 589 - 604.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
Y. Sakata, B. D. Hoit, S. B. Liggett, R. A. Walsh, and G. W. Dorn II
Decompensation of Pressure-Overload Hypertrophy in G{alpha}q-Overexpressing Mice
Circulation, April 21, 1998; 97(15): 1488 - 1495.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
G. Hasenfuss
Alterations of calcium-regulatory proteins in heart failure
Cardiovasc Res, February 1, 1998; 37(2): 279 - 289.
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 Cardiovasc ResHome page
A. D Wickenden, R. Kaprielian, Z. Kassiri, J. N Tsoporis, R. Tsushima, G. I Fishman, and P. H Backx
The role of action potential prolongation and altered intracellular calcium handling in the pathogenesis of heart failure
Cardiovasc Res, February 1, 1998; 37(2): 312 - 323.
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 Cardiovasc ResHome page
R. M Phillips, P. Narayan, A. M Gomez, K. Dilly, L. R Jones, W.J. Lederer, and R. A Altschuld
Sarcoplasmic reticulum in heart failure: central player or bystander?
Cardiovasc Res, February 1, 1998; 37(2): 346 - 351.
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 Cardiovasc ResHome page
M. A Movsesian and R. H.G Schwinger
Calcium sequestration by the sarcoplasmic reticulum in heart failure
Cardiovasc Res, February 1, 1998; 37(2): 352 - 359.
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 Cardiovasc ResHome page
M. Meyer and W. H Dillmann
Sarcoplasmic reticulum Ca2+-ATPase overexpression by adenovirus mediated gene transfer and in transgenic mice
Cardiovasc Res, February 1, 1998; 37(2): 360 - 366.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
P. P de Tombe
Altered contractile function in heart failure
Cardiovasc Res, February 1, 1998; 37(2): 367 - 380.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
K. Nagata, R. Liao, F. R Eberli, N. Satoh, B. Chevalier, C. S Apstein, and T. M Suter
Early changes in excitation-contraction coupling: transition from compensated hypertrophy to failure in Dahl salt-sensitive rat myocytes
Cardiovasc Res, February 1, 1998; 37(2): 467 - 477.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
K. R Sipido, T. Stankovicova, W. Flameng, J. Vanhaecke, and F. Verdonck
Frequency dependence of Ca2+ release from the sarcoplasmic reticulum in human ventricular myocytes from end-stage heart failure
Cardiovasc Res, February 1, 1998; 37(2): 478 - 488.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
G.A. Ng, S. M Cobbe, and G. L Smith
Non-uniform prolongation of intracellular Ca2+ transients recorded from the epicardial surface of isolated hearts from rabbits with heart failure
Cardiovasc Res, February 1, 1998; 37(2): 489 - 502.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
H. A.A. van Heugten, M. C. van Setten, K. Eizema, P. D. Verdouw, and J. M.J. Lamers
Sarcoplasmic reticulum Ca2+ ATPase promoter activity during endothelin-1 induced hypertrophy of cultured rat cardiomyocytes
Cardiovasc Res, February 1, 1998; 37(2): 503 - 514.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
A. R.W. Money-Kyrle, C. H. Davies, H. K. Ranu, P. O'Gara, N. Singh Kent, P. A. Poole-Wilson, and S. E. Harding
The role of cAMP in the frequency-dependent changes in contraction of guinea-pig cardiomyocytes
Cardiovasc Res, February 1, 1998; 37(2): 532 - 540.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
X. Sun and Y.-C. Ng
Effects of norepinephrine on expression of IGF-1/IGF-1R and SERCA2 in rat heart
Cardiovasc Res, January 1, 1998; 37(1): 202 - 209.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
C. F. McTiernan, B. H. Lemster, C. Frye, S. Brooks, A. Combes, and A. M. Feldman
Interleukin-1ß Inhibits Phospholamban Gene Expression in Cultured Cardiomyocytes
Circ. Res., October 19, 1997; 81(4): 493 - 503.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
D. D. D'Angelo, Y. Sakata, J. N. Lorenz, G. P. Boivin, R. A. Walsh, S. B. Liggett, and G. W. Dorn II
Transgenic Galpha q overexpression induces cardiac contractile failure in mice
PNAS, July 22, 1997; 94(15): 8121 - 8126.
[Abstract] [Full Text] [PDF]


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