Myocardial Gene Expression of Regulators of Myocyte Apoptosis and Myocyte Calcium Homeostasis During Hemodynamic Unloading by Ventricular Assist Devices in Patients With End-Stage Heart Failure

Bartling, Babett; Milting, Hendrik; Schumann, Heinrich; Darmer, Dorothea; Arusoglu, Latif; Koerner, Michael M.; El‐Banayosy, Aly; Koerfer, Reiner; Holtz, Juergen; Zerkowski, Hans‐Reinhard

doi:10.1161/01.cir.100.suppl_2.ii-216

Cited by 121 publications

(70 citation statements)

References 29 publications

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“…Upregulation of Bcl-x L was demonstrated after LVAD, suggesting that susceptibility to apoptosis is decreased upon unloading [115]. Also data from our group support the notion of reduced apoptotic index after mechanical support [108].…”

Section: Apoptosis and Ventricular Unloadingsupporting

confidence: 81%

See 1 more Smart Citation

Morphological and molecular changes of the myocardium after left ventricular mechanical support

Baba

Wohlschlaeger

2008

Journal of Molecular and Cellular Cardiology

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Section: Apoptosis and Ventricular Unloadingsupporting

confidence: 81%

“…The myocardial Fas system (APO-1/CD95) was shown to respond very sensitive and promptly to ventricular pressure-and volume changes [114]. After unloading, the expression of the anti-apoptotic protein FasExo6Del is decreased, hence decreased cardiomyocyte susceptibility to apoptosis can be assumed [115].…”

Section: (Extrinsic) Death Receptor Pathwaymentioning

confidence: 99%

Morphological and molecular changes of the myocardium after left ventricular mechanical support

Baba

Wohlschlaeger

2008

Journal of Molecular and Cellular Cardiology

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“…NF-κB is abundantly detected in the cardiomyocytes of the failing heart and significantly decreases after LVAS support. 34 Altered activity of mitogen activated protein kinase families, such as ERKs, JNK, p38, and Akt, after LVAS support have been reported. 33 These kinases show a sensitivity to mechanical stress of the myocardium and the changes may contribute to the favorable effect of LVAS support on myocardial apoptosis and hypertrophy.…”

Section: Mechanism Of Functional Recoverymentioning

confidence: 99%

“…LVAS unloading resulted in overexpression of the anti-apoptotic proteins, Bcl-2 and Bcl-xL. 32,34 NF-κB is known to be associated with regulation of factors involved in the pathogenesis of CHF, including IL-6, TNF-α, Bcl-XL and hemo-oxygenase-1. NF-κB is abundantly detected in the cardiomyocytes of the failing heart and significantly decreases after LVAS support.…”

Section: Mechanism Of Functional Recoverymentioning

confidence: 99%

Myocardial Recovery by Mechanical Unloading With Left Ventricular Assist System

Matsumiya

Saitoh

Sakata

et al. 2009

Circ J

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dvanced congestive heart failure (CHF) has been generally believed to be progressive and associated with substantial morbidity and mortality. 1 Cardiac transplantation has been the only curative treatment for end-stage CHF, but the number of heart transplantation is severely limited, especially in Japan. Instead, there has been increasing application of left ventricular assist systems (LVAS) for the treatment of severe CHF. 2 The LVAS consists of an electrically or pneumatically driven pump, installed either extra-or intra-corporeally. The main purpose of the LVAS is a "bridge to transplantation", but recent refinements in the engineering of the devices have enabled long-term use as "destination therapy". 3 The pump transports blood from the left ventricle (LV) to the ascending aorta, thereby restoring the systemic circulation to normal. Moreover, the pump provides potent pressure and volume unloading of the LV. These favorable effects have lead to a new indication for the use of LVAS, because there is increasing evidence that mechanical unloading with the LVAS occasionally reverses the progress of CHF and permits device explantation. [4][5][6][7] This "bridge to recovery" with the LVAS is an attractive strategy for the treatment of patients with severe CHF for whom heart transplantation or permanent LVAS use has been the only treatment option. Interest relates not only to the treatment of severe CHF, 8-10 but also to the study of the mechanisms involved in the remodeling process and its regression (ie, "reverse remodeling"). The pathophysiological mechanisms involved in the reverse remodeling induced by mechanical unloading have become a focus of intense research, with the hope of establishing reliable indicators of sustained recovery and strategies to enhance this process. 8,9 Clinically, there still exist many questions about the application of this strategy. The evaluation of LV function while on the LVAS and the prediction of sustained recovery after device explantation have been the major concerns regarding the use of this strategy for a wider range of patients. 10,11 How to evaluate LV function and decide when LVAS explantation is performed are the focus of studies. 6,10,12 Furthermore, to promote the recovery process, pharmacological, 4,7 surgical 13,14 or cell-based therapies, 15,16 combined with LVAS, are under intense investigation. In Japan, the donor supply is severely limited and almost all patients on LVAS are waiting nearly 3 years for a heart transplant. 2 Therefore, we have been forced to adopt more generous criteria for LVAS weaning compared with those used in studies from other countries. Based on this, we evaluated the factors that predict successful explantation of the LVAS and sustained functional LV recovery to determine if we can expand the population of patients who can benefit from the LVAS as a bridge to recovery. Both the clinical and laboratory findings, including our own of bridge to recovery experience with mechanical circulatory support, are reviewed. Clinical ObservationsAn earl...

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“…10,14,18,23 These findings are supported by the reversal of the Bcl-2/Bax ratio in the heart after left ventricular assist device placement. 29 It has been suggested that the cardiac myocyte could also use an alternative apoptotic pathway that activates downstream caspases via "death receptors" (eg, Fas, tumor necrosis factor [TNF] receptor) and caspase-8. 32,37 Expression of the death receptor Fas is upregulated in cardiac myocytes during myocardial ischemia and heart failure, 23,25,37,53 and increased levels of soluble Fas ligand and TNF-␣ have been reported in patients with end-stage heart failure.…”

Section: Regulation Of Cardiac Apoptosismentioning

confidence: 99%

A critical review of the literature

Scandellari¹

Social Alarms to Telecare

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W hen the concept of apoptosis was introduced in the 1970s, 1 it attracted only limited attention. However, less than two decades ago, Horvitz and colleagues 2-4 identified its essential genetic components in the roundworm, Caenorhabditis elegans, and apoptosis emerged as a significant research front. The explosion of knowledge that took place is represented by the accumulation of Ͼ25 000 studies in the last 5 years alone. It is now clear that apoptosis is an important aspect of normal organ development and cellular regulation and that it plays a role in a wide variety of physiological and pathological conditions. However, there is still much debate and controversy concerning the role of apoptosis in heart failure. To address the issues of its presence in, significance for, and overall contribution to heart failure, we will review the currently available literature and then discuss its implications for future research and treatment strategies in heart failure.

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Myocardial Gene Expression of Regulators of Myocyte Apoptosis and Myocyte Calcium Homeostasis During Hemodynamic Unloading by Ventricular Assist Devices in Patients With End-Stage Heart Failure

Cited by 121 publications

References 29 publications

Morphological and molecular changes of the myocardium after left ventricular mechanical support

Morphological and molecular changes of the myocardium after left ventricular mechanical support

Myocardial Recovery by Mechanical Unloading With Left Ventricular Assist System

A critical review of the literature

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