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(Circulation Research. 1995;77:759-764.)
© 1995 American Heart Association, Inc.

Articles

Differential Changes in Cardiac Phospholamban and Sarcoplasmic Reticular Ca²⁺-ATPase Protein Levels

Effects on Ca²⁺ Transport and Mechanics in Compensated Pressure-Overload Hypertrophy and Congestive Heart Failure

Eva Kiss, Nancy A. Ball, Evangelia G. Kranias, Richard A. Walsh

From the Department of Pharmacology and Cell Biophysics (E.K., E.G.K.) and the Division of Cardiology (N.A.B., R.A.W.), University of Cincinnati (Ohio) College of Medicine.

Correspondence to Richard A. Walsh, Division of Cardiology, University of Cincinnati College of Medicine, 231 Bethesda Ave, Cincinnati, OH 45267-0542.

	Abstract

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Abstract The objective of this study was to elucidate the role of the sarcoplasmic reticulum (SR) in the transition from compensated pressure-overload hypertrophy (increased left ventricular [LV] mass, normal LV function, and no pulmonary congestion) to congestive heart failure (increased LV mass, depressed LV function, and pulmonary congestion). To address this issue, the descending thoracic aorta was banded for 4 and 8 weeks in adult guinea pigs, and the changes in isovolumic LV mechanics, SR Ca²⁺ transport, and SR protein levels were determined and compared with age-matched sham-operated control animals. A subgroup of the 8-week banded animals manifested the congestive heart failure phenotype with diminished developed LV pressure normalized by LV mass, reduced rates of LV pressure development and relaxation, and markedly increased lung weight–to–body weight ratios. The cardiac mechanical and morphometric changes were associated with depressed protein levels of the SR Ca²⁺-ATPase (85% of the control) and phospholamban (65% of the control) assessed by quantitative immunoblotting. Resultant rates of SR Ca²⁺ uptake (V_max) and the affinity of SR Ca²⁺-ATPase for Ca²⁺ (EC₅₀) were significantly depressed [32±6 nmol Ca²⁺ · min^-1 · mg^-1 and 0.59±0.12 (µmol/L)/L, respectively] compared with the 8-week sham-operated control animals [40±1 nmol Ca²⁺ · min^-1 · mg^-1 and 0.40±0.05 (µmol/L)/L, respectively]. We conclude that this model of pressure overload–induced cardiac failure is associated with (1) diminished LV force development, rates of pressure development, and decay; (2) depressed protein expression of the Ca²⁺-cycling proteins SR Ca²⁺-ATPase and phospholamban; and (3) decreased V_max and affinity of the SR Ca²⁺-ATPase for Ca²⁺. These findings implicate these Ca²⁺-cycling proteins in the pathogenesis of congestive heart failure.

Key Words: heart failure • sarcoplasmic reticulum • Ca²⁺ pump • phospholamban • cardiac mechanics

	Introduction

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Ventricular hypertrophy is an initial adaptive process wherein increases in cardiac volume and mass occur in response to a variety of physiological and pathological stimuli. Most common among these is pressure-overload hypertrophy consequent to systemic hypertension. The altered chamber mass and geometry associated with this process initially permit the LV to favorably adapt to increased external work by normalizing chamber wall stress.¹ If the increase in LV pressure persists, alterations in systolic and diastolic chamber muscle and myocyte properties eventuate in congestive heart failure^{2 3} by mechanisms that remain poorly understood. It has been proposed that abnormal myocardial Ca²⁺ handling may be responsible, at least in part, for the impaired diastolic and systolic function in the failing heart.⁴ In cardiac tissue, the most important regulator of Ca²⁺ homeostasis is the SR, which serves as a sink for Ca²⁺ ions during relaxation and as a Ca²⁺ source during contraction. The important proteins in the SR membrane, which regulate Ca²⁺ uptake, are the Ca²⁺-ATPase and phospholamban. The SR Ca²⁺-ATPase transports Ca²⁺ from the cytosol to the lumen of the SR at the cost of ATP.⁵ Phospholamban has been shown to regulate the Ca²⁺-ATPase activity by phosphorylation/dephosphorylation.^{5 6} The dephosphorylated form of phospholamban has been suggested to inhibit the SR Ca²⁺-ATPase through a decrease in the affinity of the enzyme for Ca²⁺, and phosphorylation of phospholamban relieves this inhibition.^{5 7} Increases in ³²P incorporation into phospholamban in intact beating hearts upon isoproterenol stimulation were associated with elevated rates of Ca²⁺ uptake into SR membrane vesicles and SR Ca²⁺-ATPase activity, and these changes correlated with increases in LV functional parameters.^{7 8} In the present study, we tested the hypothesis that alterations in the SR Ca²⁺-ATPase and phospholamban protein expression levels contribute to alterations in cardiac SR function and contractility in the transition between compensated hypertrophy and heart failure in an animal model that clearly manifests these two phenotypes.

	Materials and Methods

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Preparation of Animals
Chronic pressure overload was produced in adult male Charles River guinea pigs (250 to 300 g) by subtotal descending thoracic aortic banding. After induction of sodium pentobarbital anesthesia (25 mg/kg IP), under sterile conditions, the descending thoracic aorta was exposed through an intercostal incision. A uniform degree of constriction around the descending thoracic aorta was produced by tying a 2-0 surgical silk ligature tightly around a 6-mm length of hypodermic tubing having an external diameter of 1.24 mm. The tubing was then withdrawn from the ligature, and the chest incision was surgically closed. Preliminary data from our laboratory indicated that this approach produces an initial aortic gradient of <15 mm Hg and is without histological evidence for myocardial damage. Sham-operated control animals also underwent the same operation, but the aorta was not banded. Aortic-banded animals and sham-operated control animals were housed and fed under identical conditions and were used 4 or 8 weeks after surgery. All of the surgery was performed by the same investigator, and <10% operative and long-term mortality was observed in the banded animals.

Heart Perfusion
Guinea pigs were anesthetized with intraperitoneal sodium pentobarbital (50 mg/kg) and heparinized. Hearts were quickly excised and perfused by the Langendorff method with a modified Krebs-Henseleit buffer containing (mmol/L) NaCl 113.8, KCl 4.7, MgSO₄ 1.1, KH₂PO₄ 0.12, NaHCO₃ 23.6, CaCl₂ 2.5, mannitol 6.0, and glucose 11.0. The solution was saturated with 95% O₂/5% CO₂ (pH 7.4) at 37°C. A saline-filled latex balloon attached to a 3F micromanometer catheter (Millar Instruments) was inserted into the LV via the mitral annulus for pressure measurements. The balloon was inflated to achieve 10 mm Hg initial minimum diastolic pressure and was kept isovolumic during the perfusion. Heart rate and aortic and LV pressures were continuously monitored on a Hewlett-Packard multichannel recorder interfaced to an IBM computer. Analog signals were digitized on-line at a sampling frequency of 1000 Hz, and hemodynamic parameters were derived by software developed in our laboratory. Ten to 15 beats were averaged for each condition, and premature contractions were excluded from analysis. The maximal rate of pressure development (+dP/dt_max) was calculated and used as an index of LV contractility, whereas the minimum rate (-dP/dt_min) was chosen to follow changes in the rate of isovolumic relaxation. In addition to dP/dt values, TPP and RT1/2 were also quantified. Since these temporal values of contraction and relaxation are determined by the rate of pressure development, the rate of decay, and DP, the values were normalized as TPP_c (TPP/DPx10^-1) and RT1/2_c (RT1/2/DPx10^-1). The coronary flow rate, controlled by a peristaltic pump, was adjusted to 10 mL · min^-1 · g^-1 heart wet weight and was kept constant throughout the experiment.

Western Blots
The phospholamban monoclonal antibody was purchased from Upstate Biotechnology Inc. The Ca²⁺-ATPase antibody was generated in rabbits using an oligopeptide based on the portion of the primary amino acid sequence (192 to 205) of the cardiac SR Ca²⁺-ATPase. The relative protein levels of Ca²⁺-ATPase and phospholamban in cardiac homogenates from aortic-banded and sham-operated control guinea pigs were estimated by using quantitative immunoblotting. Cardiac homogenate proteins were separated by SDS-PAGE⁹ by using 10% to 20% gradient slab gels and transferred to nitrocellulose membranes. Cardiac tissue from six guinea pigs was pooled together and used as an internal control on each gel. Transblots were reacted with phospholamban (1:1000 dilution) or Ca²⁺-ATPase antibody (1:500 dilution) and visualized by using 35S-labeled anti-mouse or anti-rabbit secondary antibodies, respectively (Amersham). The degree of labeling was determined by Phosphorimager (Molecular Dynamics) and a computer program (IMAGEQUANT), and it was expressed in relative Phosphorimager units (pixel values) per milligram cardiac homogenate protein.

The radioactivity associated with phospholamban was linear in the range of 12.5 to 50 µg homogenate protein loaded onto the gel lanes; the corresponding linear range for the SR Ca²⁺-ATPase was between 5 and 20 µg homogenate protein (Fig 1).

View larger version (14K): [in this window] [in a new window]   Figure 1. Linear range of phospholamban () and SR Ca2+-ATPase () detection in Western blots. Increasing amounts of cardiac homogenate (12.5 to 50 µg for phospholamban and 5 to 20 µg for Ca2+-ATPase) were electrophoresed, and the immunoblots were reacted with 35S-labeled anti-mouse or anti-rabbit secondary antibody, respectively. Values represent the mean±SEM of three hearts, each assayed in triplicate.

SR Ca²⁺ Transport
Cardiac tissue was homogenized in 5 vol ice-cold 10 mmol/L imidazole buffer (pH 7.0) containing 0.3 µmol/L sucrose, 10 mmol/L sodium metabisulfite, 1 mmol/L dithiothreitol, and 0.3 mmol/L phenylmethylsulfonyl fluoride. Oxalate-supported SR Ca²⁺ uptake rates were determined in LV homogenates¹⁰ with the Millipore filtration technique at 37°C using ⁴⁵CaCl₂, as previously described.¹¹ The rates of SR Ca²⁺ uptake were calculated by the least-squares linear regression analyses of the 30-, 60-, and 90-second values of Ca²⁺ uptake. The initial rates of SR Ca²⁺ uptake were linear, with cardiac homogenate protein concentration up to 100 µg. Free Ca²⁺ concentrations for the Ca²⁺ uptake were calculated by a computer program.¹²

In Vitro Back-Phosphorylation of SR Proteins
In vitro back-phosphorylation experiments were performed by use of guinea pig LV homogenates (25 µg protein) from each animal group. The samples were phosphorylated at 30°C for 2 minutes in a final volume of 25 µL under the following conditions: 50 mmol/L phosphate buffer (pH 7.0), 10 mmol/L MgCl₂, 0.5 mmol/L EGTA, 1 µmol/L okadaic acid, 30 U of the catalytic subunit of cAMP-dependent protein kinase, and 100 µmol/L [-³²P]ATP (1000 cpm/pmol). Reactions were stopped with SDS stop buffer containing 50 mmol/L Tris-HCl (pH 6.8), 2% SDS, 2% ß-mercaptoethanol, 20% glycerol, and 1% bromophenol blue. The samples (some of them boiled) were loaded onto 15% polyacrylamide gels. After electrophoresis and autoradiography, a band corresponding to phospholamban was identified on the basis of its characteristic mobility shift in SDS-PAGE upon boiling the samples before electrophoresis. The ³²P incorporation into phospholamban was calculated as pixel value (PHOSPHORIMAGER unit per milligram protein) by using the PHOSPHORIMAGER and IMAGEQUANT computer analysis program.

Other Procedures
The protein concentration was measured by the method of Peterson,¹³ with bovine serum albumin used as standard. Data are presented as mean±SEM. Statistical analyses were performed by using least-squares linear regression and ANOVA when appropriate. Comparisons were made using the Newman-Keuls multiple-range test. Values with P<.05 were regarded as statistically significant.

	Results

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Effect of Aortic Banding on LV Function
The animals in both the aortic-banded and sham-operated groups were killed at 4 and 8 weeks after surgery. The LV weight–to–body weight ratio was equivalently increased in the 4- and 8-week aortic-banded animals compared with the respective sham-operated control animals (Table 1), suggesting LV hypertrophy. Examination of the lung weight–to–body weight ratio, which was regarded as an index of pulmonary congestion and cardiac failure, revealed that this parameter did not change significantly in the 4-week banded guinea pigs but increased markedly in a subgroup of the 8-week banded guinea pigs. On the basis of the lung weight–to–body weight ratio, the 8-week banded animals, although subjected to similar intensity and duration of mechanical overload, were divided into compensated hypertrophic and decompensated pulmonary congestive subgroups.

View this table: [in this window] [in a new window]   Table 1. Effect of Aortic Banding on Morphometry

To examine the functional consequences of aortic banding and to determine the changes in LV functional parameters, the hearts of each animal were perfused in a Langendorff apparatus. No significant difference was observed in the basal nonstimulated cardiac functional parameters between the compensated hypertrophic (4- and 8-week aortic-banded) and the respective sham-operated (control) animals. By contrast, contractility (+dP/dt_max), DP, speed of relaxation (-dP/dt_min), TPP_c, and RT1/2_c were depressed significantly in the pulmonary congestive group compared with all other animal groups (Table 2).

View this table: [in this window] [in a new window]   Table 2. Effects of Aortic Banding on Isovolumic LV Mechanics

Effect of Aortic Banding on Protein Expression Levels of Phospholamban and SR Ca²⁺-ATPase
To determine whether the observed changes in the LV weight–to–body weight ratio and cardiac function were associated with altered expression of the SR Ca²⁺-ATPase and phospholamban in aortic-banded guinea pig hearts, the relative levels of these proteins were determined by quantitative immunoblotting (Fig 2). No significant change was found in the phospholamban protein level in the 4- and 8-week banded compensated hypertrophic animals compared with the respective sham control animals. By contrast, a significant decrease was observed in the pulmonary congestive group compared with all other animal groups (Fig 3A). Parallel results were noted for the protein levels of the SR Ca²⁺-ATPase, which were depressed significantly only in the decompensated pulmonary congestive group (Fig 3B). Examination of the relative changes in SR Ca²⁺-ATPase and phospholamban protein levels in the same pulmonary congestive animals revealed that the decreases in the phospholamban levels were greater than the decreases in the SR Ca²⁺-ATPase levels.

View larger version (67K): [in this window] [in a new window]   Figure 2. Autoradiogram of immunoblots of cardiac homogenates from control and 8-week aortic-banded guinea pigs with pulmonary congestion (PC). The linear range was used to determine relative changes in the protein levels of phospholamban (PLB) and SR Ca2+-ATPase.

View larger version (16K): [in this window] [in a new window]   Figure 3. Relative protein levels of phospholamban (A) and SR Ca2+-ATPase (B) in control (4- and 8-week sham-operated [Sh]), aortic-banded (4- and 8-week), and 8-week aortic-banded with pulmonary congestion (PC) guinea pig hearts were determined by quantitative immunoblotting, as described in "Materials and Methods." Data are expressed in relative PHOSPHORIMAGER units (pixel values) per milligram protein. Each value represents the mean±SEM of at least five different hearts, each assayed in triplicate. *P<.05 compared with control values.

Effect of Aortic Banding on SR Ca²⁺ Transport
To examine whether the changes in LV function and phospholamban and SR Ca²⁺-ATPase protein expression levels were associated with altered SR function in the pulmonary congestive group, the ATP-dependent oxalate-facilitated Ca²⁺ uptake was determined. Cardiac homogenates from pulmonary congestive and sham-operated animals were used, and Ca²⁺ uptake was assayed at various Ca²⁺ concentrations similar to those occurring in the myocyte during relaxation and contraction. Analyses of the Ca²⁺ transport data indicated that the highest rates of SR Ca²⁺ uptake (V_max) were significantly depressed (32±6 nmol Ca²⁺ · min^-1 · mg^-1) in the pulmonary congestive group compared with the 8-week sham-operated control group (40±1 nmol Ca²⁺ · min^-1 · mg^-1), as shown in Fig 4. The concentrations of Ca²⁺ yielding half-maximal uptake rates (EC₅₀) by the cardiac SR were 0.59±0.12 and 0.40±0.05 µmol/L in the pulmonary congestive and control groups, respectively. These observed alterations in SR Ca²⁺-transport properties in the pulmonary congestive group do not reflect alterations in the degree of phospholamban phosphorylation, as assessed by the back-phosphorylation technique. The extent of phospholamban phosphorylation was proportional to the levels of this protein present in each of the animal groups. By use of the back-phosphorylation technique, a linear correlation (r=.98) between the degree of phospholamban phosphorylation and the phospholamban protein levels was obtained for the five experimental groups.

View larger version (16K): [in this window] [in a new window]   Figure 4. Ca2+ dependence of oxalate-supported Ca2+ uptake by cardiac homogenates from 8-week sham-operated control (, n=6), 8-week aortic-banded (, n=3), and 8-week aortic-banded guinea pigs with heart failure (, n=5). The initial rates of SR Ca2+ uptake were measured at various free Ca2+ concentrations, as described in "Materials and Methods." Each value represents the mean±SEM of at least three different hearts, each assayed in triplicate. P<.05 compared with control values.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
In the present study, we report that compensated pressure-overload hypertrophy, after 4 and 8 weeks of aortic banding in guinea pigs, was not associated with significant changes in LV function or SR Ca²⁺-uptake rates. Moreover, the protein expression levels of SR Ca²⁺-ATPase and phospholamban did not differ significantly from the respective sham-operated control animals. By contrast, pulmonary congestion observed in some of the 8-week banded animals resulted in significant decreases in the contractile parameters of isovolumic cardiac mechanics. The depressed ventricular function was associated with significant decreases in the rates of Ca²⁺ transport by the SR membranes. Since the duration and intensity of mechanical overload were the same in the 8-week banded group, altered abundance and resultant function of the SR Ca²⁺ cycling proteins may be causally related to the heart failure phenotype. Our data on SR function are in agreement with previous studies that reported decreases in SR Ca²⁺ transport in different animal models of heart failure.^{14 15 16} However, in human heart failure, the findings have been controversial, indicating either no changes^{17 18} or decreases in SR Ca²⁺ transport.^{19 20} The decreased rates of SR Ca²⁺ transport in failing guinea pig hearts were associated with decreases in the SR Ca²⁺-ATPase protein levels. Similar decreases in mRNA steady state levels of this Ca²⁺ cycling protein have previously been observed in other mammalian species^{15 16 21 22 23} and in humans with end-stage cardiomyopathic congestive heart failure.^{24 25 26} Examination of the phospholamban protein levels in the same failing guinea pig hearts revealed significant decreases in the pulmonary congestive animals compared with their sham-operated controls. However, previous studies on phospholamban mRNA expression levels in animal models have reported conflicting findings.^{21 22} In pressure-overloaded rabbits, based on the steady-state mRNA levels, a significant decline was observed relative to control hearts, whereas there was no significant change in the phospholamban mRNA expression in failing hearts of aortic-banded rats compared with sham controls.²² In end-stage human heart failure, several studies have demonstrated decreased levels of phospholamban mRNA.^{25 26} However, a recent study suggested that there were no alterations in either the phospholamban or SR Ca²⁺-ATPase protein levels in microsomes prepared from the LVs of failing human hearts.²⁷

The complex regulation of the SR Ca²⁺ transport in cardiac failure is still not fully understood. In decompensated hypertrophy, we observed a significant decrease in phospholamban protein expression in guinea pig hearts. The depressed expression of phospholamban, the inhibitor of the SR Ca²⁺ pump, would be expected to result in stimulation of the affinity of the SR Ca²⁺-ATPase for Ca²⁺ and increases in Ca²⁺ transport. However, we observed decreases in the cardiac SR properties of the pulmonary congestive animals that were not due to alterations in the phosphorylation status of phospholamban in these hearts. These decreases may reflect changes in the composition of SR phospholipids,^{28 29 30} which may be associated with alterations in the micro-environment of the SR Ca²⁺-ATPase and thus override the regulatory effects of phospholamban.

In summary, our data indicate that cardiac failure produced by descending thoracic aortic banding in guinea pigs is associated with (1) depressed LV contractility and speed of relaxation, (2) decreased protein expression of phospholamban and SR Ca²⁺-ATPase, and (3) decreases in V_max and affinity of the SR Ca²⁺-ATPase for Ca²⁺. These critical components of the Ca²⁺ cycling system may be responsible in part for the transitions between compensated pressure-overload hypertrophy and congestive heart failure. Furthermore, alterations in the levels of the SR Ca²⁺-release channel similar to those observed in failing dog hearts,³¹ in human ischemic cardiomyopathy,³² and in Ca²⁺ cycling proteins in the myofibrils and sarcolemma may also contribute to the development of the heart failure phenotype.

	Selected Abbreviations and Acronyms

 

DP = developed pressure LV = left ventricle, left ventricular RT1/2 = time to half-relaxation RT1/2c = normalized RT1/2 SR = sarcoplasmic reticulum TPP = time to peak pressure TPPc = normalized TPP

	Acknowledgments

 
This study was supported by National Institutes of Health grants SCOR P50-HL-52318, HL-33579, HL-206057, and HL-22619. We are grateful to Dr Donald G. Ferguson for the SR Ca²⁺-ATPase peptide used to make the Ca²⁺-ATPase polyclonal antibody.

Received September 28, 1994; accepted July 12, 1995.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 
1. Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975;56:56-64.

2. Siri FM, Nordin C, Factor SM, Sonnenblick E, Aronson R. Compensatory hypertrophy and failure in gradual pressure-overload guinea pig heart. Am J Physiol. 1989;257:H1016-H1024. [Abstract/Free Full Text]

3. Capasso JM, Palackal T, Olivetti G, Anversa P. Left ventricular failure induced by long-term hypertension in rats. Circ Res. 1990;66:1400-1412. [Abstract/Free Full Text]

4. Gwathmey JK, Copelas L, MacKinnon R, Schoen FJ, Feldman MD, Grossman W, Morgan JP. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res. 1987;61:70-76. [Abstract/Free Full Text]

5. Edes I, Kranias EG. Regulation of cardiac sarcoplasmic reticulum function by phospholamban. Membr Biochem. 1989;7:175-192.

6. Simmerman HKB, Collins JH, Theibert JL, Wegener AD, Jones LR. Sequence analysis of phospholamban: identification of phosphorylation sites and two major structural domains. J Biol Chem. 1986;261:13333-13341. [Abstract/Free Full Text]

7. Lindemann JP, Jones LR, Hathaway DR, Henry BG, Watanabe AM. ß-Adrenergic stimulation of phospholamban phosphorylation and Ca²⁺-ATPase activity in guinea pig ventricles. J Biol Chem. 1983;260:4516-4525. [Abstract/Free Full Text]

8. Kranias EG, Garvey JL, Srivastava RD, Solaro RJ. Phosphorylation and functional modifications of sarcoplasmic reticulum and myofibrils in isolated rabbit hearts stimulated with isoprenaline. Biochem J. 1985;226:113-121. [Medline] [Order article via Infotrieve]

9. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680-685. [Medline] [Order article via Infotrieve]

10. Feher JJ, Briggs FN, Hess ML. Characterization of cardiac sarcoplasmic reticulum from ischemic myocardium: comparison of isolated sarcoplasmic reticulum with unfractionated homogenates. J Mol Cell Cardiol. 1980;12:427-432. [Medline] [Order article via Infotrieve]

11. Kim HW, Steenart NAE, Ferguson DG, Kranias EG. Functional reconstitution of the cardiac sarcoplasmic reticulum Ca²⁺-ATPase with phospholamban in phospholipid vesicles. J Biol Chem. 1990;265:1702-1709. [Abstract/Free Full Text]

12. Robertson S, Potter JD. The use of metal buffers in biological systems. Methods Pharmacol. 1984;5:63-75.

13. Peterson GL. A simplification of the protein assay method of Lowry et al, which is more generally applicable. Anal Biochem. 1977;83:346-356. [Medline] [Order article via Infotrieve]

14. Lamers JHJ, Stinis JT. Defective calcium pump in the sarcoplasmic reticulum of the hypertrophied rabbit heart. Life Sci. 1979;24:2313-2320. [Medline] [Order article via Infotrieve]

15. de la Bastie D, Levitsky D, Rappaport L, Mercadier J-J, Marotte F, Wisnewsky C, Brovkovich V, Schwartz K, Lompré AM. Function of the sarcoplasmic reticulum and expression of its Ca²⁺-ATPase gene in pressure overload–induced cardiac hypertrophy in the rat. Circ Res. 1990;66:554-564. [Abstract/Free Full Text]

16. Edes I, Talosi L, Kranias EG. Sarcoplasmic reticulum function in normal heart and in cardiac disease. Heart Failure. 1990-1991;6:221-237.

17. Movsesian MA, Bristow MR, Krall J. Calcium uptake by cardiac sarcoplasmic reticulum from patients with idiopathic dilated cardiomyopathy. Circ Res. 1987;65:1141-1144. [Abstract/Free Full Text]

18. Movsesian MA, Colyer J, Wanf JH, Krall J. Phospholamban-mediated stimulation of Ca²⁺ uptake in sarcoplasmic reticulum from normal and failing hearts. J Clin Invest. 1990;85:1698-1702.

19. Limas CJ, Olivari MT, Goldenberg TB, Benditt DG, Simon A. Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy. Cardiovasc Res. 1987;21:601-605. [Medline] [Order article via Infotrieve]

20. Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, Holubarsch C, Posival H, Just H, Drexler H. Relation between myocardial function and expression of sarcoplasmic reticulum Ca²⁺-ATPase in failing and nonfailing human myocardium. Circ Res. 1994;75:434-442. [Abstract/Free Full Text]

21. Nagai R, Zarain-Herzberg A, Brandl C, Fujii J, Tada M, MacLennan DH, Alpert NR, Periasamy M. Regulation of myocardial Ca²⁺-ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone. Proc Natl Acad Sci U S A. 1989;86:2966-2970. [Abstract/Free Full Text]

22. Feldman AM, Weinberg EO, Ray PE, Lorell BH. Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. Circ Res. 1993;73:184-192. [Abstract]

23. Rockman HA, Ono S, Ross RS, Jones LR, Karimi M, Bhargava V, Ross J Jr, Chien KR. Molecular and physiological alterations in murine ventricular dysfunction. Proc Natl Acad Sci U S A. 1994;91:2694-2698. [Abstract/Free Full Text]

24. Arai M, Alpert NR, MacLennan DH, Barton P, Periasamy M. Alterations in sarcoplasmic reticulum gene expression in human heart failure: a possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. Circ Res. 1993;72:463-469. [Abstract/Free Full Text]

25. Mercadier J, Lompré AM, Duc P, Boheler KR, Fraysse JB, Wisnewsky C, Allen PD, Komajda M, Schwartz K. Altered sarcoplasmic reticulum Ca²⁺-ATPase gene expression in the human ventricle during end-stage heart failure. J Clin Invest. 1990;85:305-309.

26. Feldman AM, Ray PE, Silan CM, Mercer JA, Minobe W, Bristow MR. Selective gene expression in failing human heart: quantification of steady-state levels of messenger RNA in endomyocardial biopsies using the polymerase chain reaction. Circulation. 1991;83:1866-1872. [Abstract/Free Full Text]

27. Movsesian MA, Karimi M, Green K, Jones LR. Ca²⁺-transporting ATPase, phospholamban, and calsequestrin labels in nonfailing and failing human myocardium. Circulation. 1994;90:653-657. [Abstract/Free Full Text]

28. Szymanska G, Kim HW, Kranias EG. Reconstitution of the skeletal sarcoplasmic reticulum Ca²⁺-pump: influence of negatively charged phospholipids. Biochim Biophys Acta. 1991;1091:127-134. [Medline] [Order article via Infotrieve]

29. Okumura K, Yamada Y, Kondo J, Hashimoto H, Ito T, Kitoh J. Decreased 1,2-diacylglycerol levels in myopathic hamster hearts during the development of heart failure. J Mol Cell Cardiol. 1991;23:409-416. [Medline] [Order article via Infotrieve]

30. Dhalla NS, Elimban V, Rupp H. Paradoxical role of lipid metabolism in heart function and dysfunction. Mol Cell Biochem. 1992;116:3-9. [Medline] [Order article via Infotrieve]

31. Vatner DE, Sato N, Kiuchi K, Shannon RP, Vatner SF. Decrease in myocardial ryanodine receptors and altered excitation-contraction coupling early in the development of heart failure. Circulation. 1994;90:1423-1430. [Abstract/Free Full Text]

32. Brillantes A-M, Allen P, Takahashi T, Izumo S, Marks AR. Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy. Circ Res. 1992;71:18-26.[Abstract/Free Full Text]

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				R. L. Schultz, J. G. Swallow, R. P. Waters, J. A. Kuzman, R. A. Redetzke, S. Said, G. M. de Escobar, and A. M. Gerdes Effects of Excessive Long-Term Exercise on Cardiac Function and Myocyte Remodeling in Hypertensive Heart Failure Rats Hypertension, August 1, 2007; 50(2): 410 - 416. [Abstract] [Full Text] [PDF]

				P. Rodriguez, B. Mitton, P. Nicolaou, G. Chen, and E. G. Kranias Phosphorylation of human inhibitor-1 at Ser67 and/or Thr75 attenuates stimulatory effects of protein kinase A signaling in cardiac myocytes Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H762 - H769. [Abstract] [Full Text] [PDF]

				S. Nattel, A. Maguy, S. Le Bouter, and Y.-H. Yeh Arrhythmogenic Ion-Channel Remodeling in the Heart: Heart Failure, Myocardial Infarction, and Atrial Fibrillation Physiol Rev, April 1, 2007; 87(2): 425 - 456. [Abstract] [Full Text] [PDF]

				A. P. Saliaris, L. C. Amado, K. M. Minhas, K. H. Schuleri, S. Lehrke, M. St. John, T. Fitton, C. Barreiro, C. Berry, M. Zheng, et al. Chronic allopurinol administration ameliorates maladaptive alterations in Ca2+ cycling proteins and beta-adrenergic hyporesponsiveness in heart failure Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1328 - H1335. [Abstract] [Full Text] [PDF]

				A. A. Armoundas, J. Rose, R. Aggarwal, B. D. Stuyvers, B. O'Rourke, D. A. Kass, E. Marban, S. R. Shorofsky, G. F. Tomaselli, and C. William Balke Cellular and molecular determinants of altered Ca2+ handling in the failing rabbit heart: primary defects in SR Ca2+ uptake and release mechanisms Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1607 - H1618. [Abstract] [Full Text] [PDF]

				P. Rodriguez, B. Mitton, J. R. Waggoner, and E. G. Kranias Identification of a Novel Phosphorylation Site in Protein Phosphatase Inhibitor-1 as a Negative Regulator of Cardiac Function J. Biol. Chem., December 15, 2006; 281(50): 38599 - 38608. [Abstract] [Full Text] [PDF]

				N. S. Dhalla, M. R. Dent, P. S. Tappia, R. Sethi, J. Barta, and R. K. Goyal Subcellular Remodeling as a Viable Target for the Treatment of Congestive Heart Failure Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2006; 11(1): 31 - 45. [Abstract] [PDF]

				M. Pavlovic, A. Schaller, B. Steiner, P. Berdat, T. Carrel, J.-P. Pfammatter, R. A. Ammann, and S. Gallati Gender Modulates the Expression of Calcium-Regulating Proteins in Pediatric Atrial Myocardium Experimental Biology and Medicine, December 1, 2005; 230(11): 853 - 859. [Abstract] [Full Text] [PDF]

				G. Colombo, S. Gatti, F. Turcatti, A. Sordi, L. R. Fassati, F. Bonino, J. M. Lipton, and A. Catania Gene Expression Profiling Reveals Multiple Protective Influences of the Peptide {alpha}-Melanocyte-Stimulating Hormone in Experimental Heart Transplantation J. Immunol., September 1, 2005; 175(5): 3391 - 3401. [Abstract] [Full Text] [PDF]

				F. Prunier, Y. Chen, B. Gellen, M. Heimburger, C. Choqueux, B. Escoubet, J.-B. Michel, and J.-J. Mercadier Left ventricular SERCA2a gene down-regulation does not parallel ANP gene up-regulation during post-MI remodelling in rats Eur J Heart Fail, August 1, 2005; 7(5): 739 - 747. [Abstract] [Full Text] [PDF]

				Q. Shao, B. Ren, H. K. Saini, T. Netticadan, N. Takeda, and N. S. Dhalla Sarcoplasmic reticulum Ca2+ transport and gene expression in congestive heart failure are modified by imidapril treatment Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1674 - H1682. [Abstract] [Full Text] [PDF]

				Y. Xu, Z. Zhang, V. Timofeyev, D. Sharma, D. Xu, D. Tuteja, P. H. Dong, G. U. Ahmmed, Y. Ji, G. E Shull, et al. The effects of intracellular Ca2+ on cardiac K+ channel expression and activity: novel insights from genetically altered mice J. Physiol., February 1, 2005; 562(3): 745 - 758. [Abstract] [Full Text] [PDF]

				J. E. J. Schultz, B. J. Glascock, S. A. Witt, M. L. Nieman, K. J. Nattamai, L. H. Liu, J. N. Lorenz, G. E. Shull, T. R. Kimball, and M. Periasamy Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1146 - H1153. [Abstract] [Full Text] [PDF]

				Y.-K. Kim, S.-J. Kim, A. Yatani, Y. Huang, G. Castelli, D. E. Vatner, J. Liu, Q. Zhang, G. Diaz, R. Zieba, et al. Mechanism of Enhanced Cardiac Function in Mice with Hypertrophy Induced by Overexpressed Akt J. Biol. Chem., November 28, 2003; 278(48): 47622 - 47628. [Abstract] [Full Text] [PDF]

				S. Huke, L. H Liu, D. Biniakiewicz, W. T Abraham, and M. Periasamy Altered force-frequency response in non-failing hearts with decreased SERCA pump-level Cardiovasc Res, September 1, 2003; 59(3): 668 - 677. [Abstract] [Full Text] [PDF]

				D. J. Lips, L. J. deWindt, D. J.W. van Kraaij, and P. A. Doevendans Molecular determinants of myocardial hypertrophy and failure: alternative pathways for beneficial and maladaptive hypertrophy Eur. Heart J., May 2, 2003; 24(10): 883 - 896. [Abstract] [Full Text] [PDF]

				S. Mishra, H. N. Sabbah, J. C. Jain, and R. C. Gupta Reduced Ca2+-calmodulin-dependent protein kinase activity and expression in LV myocardium of dogs with heart failure Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H876 - H883. [Abstract] [Full Text] [PDF]

				J. Kneller, H. Sun, N. Leblanc, and S. Nattel Remodeling of Ca2+-handling by atrial tachycardia: evidence for a role in loss of rate-adaptation Cardiovasc Res, May 1, 2002; 54(2): 416 - 426. [Abstract] [Full Text] [PDF]

				A. Nakamura, D. G. Rokosh, M. Paccanaro, R. R. Yee, P. C. Simpson, W. Grossman, and E. Foster LV systolic performance improves with development of hypertrophy after transverse aortic constriction in mice Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1104 - H1112. [Abstract] [Full Text] [PDF]

				D. J. Grieve, P. A. MacCarthy, N. P. Gall, A. C. Cave, and A. M. Shah Divergent Biological Actions of Coronary Endothelial Nitric Oxide During Progression of Cardiac Hypertrophy Hypertension, August 1, 2001; 38(2): 267 - 273. [Abstract] [Full Text] [PDF]

				U. Wisloff, J. P. Loennechen, G. Falck, V. Beisvag, S. Currie, G. Smith, and O. Ellingsen Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats Cardiovasc Res, June 1, 2001; 50(3): 495 - 508. [Abstract] [Full Text] [PDF]

				S. Y. Boateng, R. U. Naqvi, M. U. Koban, M. H. Yacoub, K. T. MacLeod, and K. R. Boheler Low-dose ramipril treatment improves relaxation and calcium cycling after established cardiac hypertrophy Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1029 - H1038. [Abstract] [Full Text] [PDF]

				C. Piper, J. Bilger, E.-M. Henrichs, H.-P. Schultheiss, D. Horstkotte, and A. Doerner Is myocardial Na+/Ca2+ exchanger transcription a marker for different stages of myocardial dysfunction? Quantitative polymerase chain reaction of the messenger RNA in endomyocardial biopsies of patients with heart failure J. Am. Coll. Cardiol., July 1, 2000; 36(1): 233 - 241. [Abstract] [Full Text] [PDF]

				Y. Takeishi, P. Ping, R. Bolli, D. L. Kirkpatrick, B. D. Hoit, and R. A. Walsh Transgenic Overexpression of Constitutively Active Protein Kinase C {epsilon} Causes Concentric Cardiac Hypertrophy Circ. Res., June 23, 2000; 86(12): 1218 - 1223. [Abstract] [Full Text] [PDF]

				G. U. Ahmmed, P. H. Dong, G. Song, N. A. Ball, Y. Xu, R. A. Walsh, and N. Chiamvimonvat Changes in Ca2+ Cycling Proteins Underlie Cardiac Action Potential Prolongation in a Pressure-Overloaded Guinea Pig Model With Cardiac Hypertrophy and Failure Circ. Res., March 17, 2000; 86(5): 558 - 570. [Abstract] [Full Text] [PDF]

				T. Netticadan, R. M. Temsah, K. Kawabata, and N. S. Dhalla Sarcoplasmic Reticulum Ca2+/Calmodulin-Dependent Protein Kinase Is Altered in Heart Failure Circ. Res., March 17, 2000; 86(5): 596 - 605. [Abstract] [Full Text] [PDF]

				Y. Takeishi, T. Jalili, B. D. Hoit, D. L. Kirkpatrick, L. E. Wagoner, W. T. Abraham, and R. A. Walsh Alterations in Ca2+ cycling proteins and G{alpha}q signaling after left ventricular assist device support in failing human hearts Cardiovasc Res, March 1, 2000; 45(4): 883 - 888. [Abstract] [Full Text] [PDF]

				M.E. Diaz, A.W. Trafford, S.C. O'Neill, and D.A. Eisner Can changes of ryanodine receptor expression affect cardiac contractility? Cardiovasc Res, March 1, 2000; 45(4): 1068 - 1069. [Full Text] [PDF]

				C. A. Walker, F. A. Crawford Jr, and F. G. Spinale MYOCYTE CONTRACTILE DYSFUNCTION WITH HYPERTROPHY AND FAILURE: RELEVANCE TO CARDIAC SURGERY J. Thorac. Cardiovasc. Surg., February 1, 2000; 119(2): 388 - 400. [Full Text] [PDF]

				T. Tanigawa, M. Yano, M. Kohno, T. Yamamoto, T. Hisaoka, K. Ono, T. Ueyama, S. Kobayashi, Y. Hisamatsu, T. Ohkusa, et al. Mechanism of preserved positive lusitropy by cAMP-dependent drugs in heart failure Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H313 - H320. [Abstract] [Full Text] [PDF]

				Y. Takeishi, J.-i. Abe, J.-D. Lee, H. Kawakatsu, R. A. Walsh, and B. C. Berk Differential Regulation of p90 Ribosomal S6 Kinase and Big Mitogen-Activated Protein Kinase 1 by Ischemia/Reperfusion and Oxidative Stress in Perfused Guinea Pig Hearts Circ. Res., December 3, 1999; 85(12): 1164 - 1172. [Abstract] [Full Text] [PDF]

				T. Jalili, Y. Takeishi, G. Song, N. A. Ball, G. Howles, and R. A. Walsh PKC translocation without changes in Galpha q and PLC-beta protein abundance in cardiac hypertrophy and failure Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2298 - H2304. [Abstract] [Full Text] [PDF]

				Y. Takeishi, T. Jalili, N. A. Ball, and R. A. Walsh Responses of Cardiac Protein Kinase C Isoforms to Distinct Pathological Stimuli Are Differentially Regulated Circ. Res., August 6, 1999; 85(3): 264 - 271. [Abstract] [Full Text] [PDF]

				E. O. Weinberg, C. D. Thienelt, S. E. Katz, J. Bartunek, M. Tajima, S. Rohrbach, P. S. Douglas, and B. H. Lorell Gender differences in molecular remodeling in pressure overload hypertrophy J. Am. Coll. Cardiol., July 1, 1999; 34(1): 264 - 273. [Abstract] [Full Text] [PDF]

				S.-J. Kim, K. Iizuka, R. A. Kelly, Y.-J. Geng, S. P. Bishop, G. Yang, A. Kudej, B. K. McConnell, C. E. Seidman, J. G. Seidman, et al. An alpha -cardiac myosin heavy chain gene mutation impairs contraction and relaxation function of cardiac myocytes Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1780 - H1787. [Abstract] [Full Text] [PDF]

				G. F. Tomaselli and E. Marban Electrophysiological remodeling in hypertrophy and heart failure Cardiovasc Res, May 1, 1999; 42(2): 270 - 283. [Full Text] [PDF]

				Y. Takeishi, A. Bhagwat, N. A. Ball, D. L. Kirkpatrick, M. Periasamy, and R. A. Walsh Effect of angiotensin-converting enzyme inhibition on protein kinase C and SR proteins in heart failure Am J Physiol Heart Circ Physiol, January 1, 1999; 276(1): H53 - H62. [Abstract] [Full Text] [PDF]

				S. Currie and G. L. Smith Enhanced phosphorylation of phospholamban and downregulation of sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in cardiac sarcoplasmic reticulum from rabbits with heart failure Cardiovasc Res, January 1, 1999; 41(1): 135 - 146. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				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]

				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. [Abstract] [Full Text] [PDF]

				B. Linck, P. Bokník, H. A. Baba, T. Eschenhagen, U. Haverkamp, E. Jäckel, L. R. Jones, U. Kirchhefer, J. Knapp, S. Läer, et al. Long-term Beta Adrenoceptor-Mediated Alteration in Contractility and Expression of Phospholamban and Sarcoplasmic Reticulum Ca++-ATPase in Mammalian Ventricle J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 531 - 538. [Abstract] [Full Text]

				G. Hasenfuss Animal models of human cardiovascular disease, heart failure and hypertrophy Cardiovasc Res, July 1, 1998; 39(1): 60 - 76. [Abstract] [Full Text] [PDF]

				E. McCall, K. S. Ginsburg, R. A. Bassani, T. R. Shannon, M. Qi, A. M. Samarel, and D. M. Bers Ca flux, contractility, and excitation-contraction coupling in hypertrophic rat ventricular myocytes Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1348 - H1360. [Abstract] [Full Text] [PDF]

				L. S. Maier, R. Brandes, B. Pieske, and D. M. Bers Effects of left ventricular hypertrophy on force and Ca2+ handling in isolated rat myocardium Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1361 - H1370. [Abstract] [Full Text] [PDF]

				I. Morii, Y. Kihara, M. Inoko, and S. Sasayama Myocardial Contractile Efficiency and Oxygen Cost of Contractility Are Preserved During Transition From Compensated Hypertrophy to Failure in Rats With Salt-Sensitive Hypertension Hypertension, April 1, 1998; 31(4): 949 - 960. [Abstract] [Full Text] [PDF]

				H. Luss, P. Bokniek, G. Heusch, F. U. Muller, J. Neumann, W. Schmitz, and R. Schulz Expression of calcium regulatory proteins in short-term hibernation and stunning in the in situ porcine heart Cardiovasc Res, March 1, 1998; 37(3): 606 - 617. [Abstract] [Full Text] [PDF]

				G. Hasenfuss Alterations of calcium-regulatory proteins in heart failure Cardiovasc Res, February 1, 1998; 37(2): 279 - 289. [Full Text] [PDF]

				S. Richard, F. Leclercq, S. Lemaire, C. Piot, and J. Nargeot Ca2+ currents in compensated hypertrophy and heart failure Cardiovasc Res, February 1, 1998; 37(2): 300 - 311. [Abstract] [Full Text] [PDF]

				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. [Abstract] [Full Text] [PDF]

				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. [Full Text] [PDF]

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

				K. Wong, K. R Boheler, J. Bishop, M. Petrou, and M. H Yacoub Clenbuterol induces cardiac hypertrophy with normal functional, morphological and molecular features Cardiovasc Res, January 1, 1998; 37(1): 115 - 122. [Abstract] [Full Text] [PDF]

				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]

				K. Paul, N. A. Ball, G. W. Dorn II, and R. A. Walsh Left Ventricular Stretch Stimulates Angiotensin II– Mediated Phosphatidylinositol Hydrolysis and Protein Kinase C {epsilon} Isoform Translocation in Adult Guinea Pig Hearts Circ. Res., November 19, 1997; 81(5): 643 - 650. [Abstract] [Full Text]

				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]

				K. Wong, K. R. Boheler, M. Petrou, and M. H. Yacoub Pharmacological Modulation of Pressure-Overload Cardiac Hypertrophy : Changes in Ventricular Function, Extracellular Matrix, and Gene Expression Circulation, October 7, 1997; 96(7): 2239 - 2246. [Abstract] [Full Text]

				F. G. Spinale, R. Mukherjee, J. P. Iannini, S. Whitebread, L. Hebbar, M. J. Clair, D. M. Melton, M. H. Cox, P. B. Thomas, and P. B. Marc de Gasparo Modulation of the Renin-Angiotensin Pathway Through Enzyme Inhibition and Specific Receptor Blockade in Pacing-Induced Heart Failure : II. Effects on Myocyte Contractile Processes Circulation, October 7, 1997; 96(7): 2397 - 2406. [Abstract] [Full Text]

				R. J. Hajjar, U. Schmidt, J. X. Kang, T. Matsui, and A. Rosenzweig Adenoviral Gene Transfer of Phospholamban in Isolated Rat Cardiomyocytes : Rescue Effects by Concomitant Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase Circ. Res., August 19, 1997; 81(2): 145 - 153. [Abstract] [Full Text]

				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]

				S. F. Khoury, B. D. Hoit, V. Dave, C. M. Pawloski-Dahm, Y. Shao, M. Gabel, M. Periasamy, and R. A. Walsh Effects of Thyroid Hormone on Left Ventricular Performance and Regulation of Contractile and Ca2+-Cycling Proteins in the Baboon: Implications for the Force-Frequency and Relaxation-Frequency Relationships Circ. Res., October 1, 1996; 79(4): 727 - 735. [Abstract] [Full Text]

				M. Jane Lalli, J. Yong, V. Prasad, K. Hashimoto, D. Plank, G. J. Babu, D. Kirkpatrick, R. A. Walsh, M. Sussman, A. Yatani, et al. Sarcoplasmic Reticulum Ca2+ ATPase (SERCA) 1a Structurally Substitutes for SERCA2a in the Cardiac Sarcoplasmic Reticulum and Increases Cardiac Ca2+ Handling Capacity Circ. Res., July 20, 2001; 89(2): 160 - 167. [Abstract] [Full Text] [PDF]

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