Patients With End-Stage Congestive Heart Failure Treated With β-Adrenergic Receptor Antagonists Have Improved Ventricular Myocyte Calcium Regulatory Protein Abundance

Kubo, Hajime; Margulies, Kenneth B.; Piacentino, Valentino; Gaughan, John; Houser, Steven R.

doi:10.1161/hc3401.095073

Cited by 125 publications

(89 citation statements)

References 48 publications

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“…Studies in isolated cells show diminished amplitudes and longer duration of calcium transients in heart failure (HF) compared to normal. (Beuckelmann et al, 1992;Gómez et al, 2001;Jiang et al, 2002;Kubo et al, 2001;O'Rourke et al, 1999) Likewise, reduced SERCA2a expression, De La Bastie et al, 1990;Kihara et al, 1991; as well as the expression of PLB (Flesch et al, 1996;Schwinger et al, 1995;Studer et al, 1994) and FKBP 12.6 (Marx et al, 2000;Yano et al, 2000) are diminished in some models of HF. However, reduced expression of SERCA2a is not a finding common across all models.…”

Section: Mechanical Dysfunction and Alternansmentioning

confidence: 99%

Cellular mechanisms of arrhythmogenic cardiac alternans

Laurita

Rosenbaum

2008

Progress in Biophysics and Molecular Biology

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Mechanical dysfunction remains as one of the best predictors of sudden cardiac death (SCD), but despite this close association the causal relationships between electrical instability and mechanical dysfunction are not fully understood. (Bigger et al., 1984;Buxton et al., 1984) Even though the effects of electrical instability on mechanical dysfunction of the heart is well appreciated and relatively clear, the reverse effects that mechanical dysfunction have electrical instability, or mechano-electrical feedback (MEF), are not. (Kohl et al., 2006;Lab, 1996) Stretch activated channels, for example, are one way mechanical activity can directly influence electrical activity at the cellular level under physiologic and pathophysiological conditions. (Hu et al., 1997) Alternatively, intracellular calcium, which regulates mechanical contraction, can significantly influence electrical function of the heart as well. The mechanisms by which intracellular calcium governs electrical instability of the heart is the main focus of this manuscript. Traditionally, calcium mediated arrhythmogenesis is associated with delayed after depolarizations and abnormal impulse formation. (Katra et al., 2007;Liu et al., 2006;Rosen, 1985;Ter Keurs et al., 2006;Wehrens et al., 2003) However, in this manuscript we focus on how cardiac alternans, a mechanisms of reentrant excitation, is another significant way mechanical dysfunction and arrhythmogenesis are causally related.Cardiac alternans can refer to either mechanical (contractile) or electrical (repolarization) oscillations that occur on an every other beat basis. Cardiac alternans has been recognized for more than 100 years. Shown in Figure 1 (Panel A) is a very early record of arterial pressure measured during a steady state heart rate, where pulse magnitude alternates on every other beat (arrows). (Traube, 1872) At this time, the ECG had not been invented; however, soon after its introduction electrical alternans was reported as well. Shown in Panel B (Figure 1) is an early example of electrical alternans as evidenced by oscillations of the ECG T-wave (arrows) and QRS. (Lewis, 1910) Soon after cardiac alternans was first reported, it was associated with a poor prognosis. (Windle, 1913) Surprisingly, at this same time several important characteristics of cardiac alternans were observed, such as alternans occurring in a structurally normal heart and appearing at faster heart rates. Subsequently, Twave alternans was more directly related to coronary artery occlusion and shown to be highly reproducible. (Hellerstein et al., 1950)

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Section: Mechanical Dysfunction and Alternansmentioning

confidence: 99%

Cellular mechanisms of arrhythmogenic cardiac alternans

Laurita

Rosenbaum

2008

Progress in Biophysics and Molecular Biology

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“…The expression and regulation of SERCA2a activity have been widely investigated, emphasizing its central role in the regulation of Ca 2+ homeostasis during development and under a variety of patho-physiological conditions [3][4][5][6]. Studies from a variety of animal models of heart disease [7][8][9] and end stage human heart failure [10,11] suggest that defects in SR Ca 2+ uptake function is one of the major contributing factors for the progression of heart failure. Several studies have demonstrated the role of SERCA2a interacting proteins in modulating pump activity and in normal and failing hearts.…”

Section: Introductionmentioning

confidence: 99%

Sarcolipin and phospholamban as regulators of cardiac sarcoplasmic reticulum Ca2+ ATPase

Bhupathy¹,

Babu²,

Periasamy³

2007

Journal of Molecular and Cellular Cardiology

118

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The cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a critical role in maintaining the intracellular calcium homeostasis during cardiac contraction and relaxation. It has been well documented over the years that altered expression and activity of SERCA2a can lead to systolic and diastolic dysfunction. The activity of SERCA2a is regulated by two structurally similar proteins, phospholamban (PLB) and sarcolipin (SLN). Although, the relevance of PLB has been extensively studied over the years, the role SLN in cardiac physiology is an emerging field of study. This review focuses on the advances in the understanding of the regulation of SERCA2a by SLN and PLB. In particular, it highlights the similarities and differences between the two proteins and their roles in cardiac patho-physiology.

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“…Recent reports have indicated that the major mechanism is correction of the abnormal dynamic state of Ca 2+ in myocardial cells by indirectly acting on SERCA2a (Ca 2+ -ATPase of cardiac sarcoplasmic reticulum), based on β 1 receptor blocking, to improve contractility. 22,24,[26][27][28][29] Moreover, findings in those studies suggested that β-blocking agents might directly act on the ryanodine receptor on the membrane of the cardiac sarcoplasmic reticulum. Another study reported that only carvedilol directly acted on ryanodine receptor 2 to selectively control arrhythmia induced by Ca 2+ release from the reticulum.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Clinical Efficacy and Adverse Effects of β-Blocking Agents Used Clinically for Chronic Heart Failure

Takayanagi

Fujito

Kimura

et al. 2017

Biological & Pharmaceutical Bulletin

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Clinical efficacy and adverse effects of the β-blocking agents, carvedilol, bisoprolol, and metoprolol were analyzed theoretically, and then compared quantitatively, for the purpose of determining their proper use for chronic heart failure. Initially, we evaluated occupancy binding to the β 1 and β 2 receptors (Фss β 1 and Фss β 2 ) by these drugs. Thereafter, we examined the relationship between Фss β 1 values and left ventricular ejection fraction (LVEF) increase rate to determine efficacy. The result showed that the efficacy with carvedilol could be attained with a lower Фss β 1 value than the others. Therefore, we constructed a model under the assumption that β-blocking agents exert both indirect action of LVEF increase through the β 1 receptor and direct action on ryanodine receptor 2. Using the model, it was suggested that these drugs have no differences in regard to the efficacy, while it was clarified theoretically that only carvedilol produces an effect that directly involves ryanodine receptor 2 at clinical doses. We also investigated decreases in heart rate and forced expiratory volume in 1 s as adverse effects of β-blocking agents using a ternary complex model. It was indicated that carvedilol is less likely to induce a heart rate decrease. Meanwhile, it was also suggested that the risk of an asthmatic attack was higher for carvedilol at clinical doses. Our results are considered useful for selection of a proper β-blocking agent and its administration at a reasonable dose for successful heart failure therapy.

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Patients With End-Stage Congestive Heart Failure Treated With β-Adrenergic Receptor Antagonists Have Improved Ventricular Myocyte Calcium Regulatory Protein Abundance

Cited by 125 publications

References 48 publications

Cellular mechanisms of arrhythmogenic cardiac alternans

Cellular mechanisms of arrhythmogenic cardiac alternans

Sarcolipin and phospholamban as regulators of cardiac sarcoplasmic reticulum Ca2+ ATPase

Analysis of Clinical Efficacy and Adverse Effects of β-Blocking Agents Used Clinically for Chronic Heart Failure

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