DOI: 10.1161/circ.100.suppl_2.ii-216. 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

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

10.1161/circ.100.suppl_2.ii-216

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation (276)

Abstract

Background —In patients with end-stage heart failure, characterized by an increased susceptibility to cardiomyocyte apoptosis and a labile cardiomyocyte calcium homeostasis, a ventricular assist device (VAD) is implanted for bridging to cardiac transplantation and results in myocardial unloading. Although phenotype changes in the failing heart are assumed to result from hemodynamic overload, the reversibility of these changes under unloading is unknown. Methods and Results —By use of quantitative reverse-transcription polymerase chain reaction, mRNA expression analyses were performed on left ventricular specimens obtained from 10 nonfailing donor hearts (from 8 patients with dilated cardiomyopathy and 2 patients with coronary heart disease) at the time of VAD implantation and 36 to 169 days later during VAD removal with subsequent cardiac transplantation. In terminally failing hearts before VAD support, left ventricular mRNA analyses revealed increased Pro-ANP, reduced antiapoptotic Bcl-x L and antiapoptotic Fas isoform FasExo6Del, and a decreased ratio of sarcoplasmic reticulum Ca 2+ -ATPase per sarcolemmal Na + -Ca 2+ exchanger in comparison with nonfailing ventricles. After VAD unloading, ventricular transcription of Pro-ANP was immediately normalized, and apoptotic DNA fragmentation was attenuated. In patients with dilated cardiomyopathy, mRNAs of Bcl-x L and FasExo6Del/Fas were enhanced depending on time on VAD. The Bcl-x L mRNA level correlated positively with that of the Bcl-x L protein. Transcription of sarcoplasmic reticulum Ca 2+ -ATPase/Na + -Ca 2+ exchanger demonstrated recovery in only 4 of 10 patients. Conclusions —Mechanical support of the failing heart induces a time-dependent change in myocardial gene expression compatible with a decreased susceptibility to apoptosis.

Bibliography

Bartling, B., Milting, H., Schumann, H., Darmer, D., Arusoglu, L., Koerner, M. M., El-Banayosy, A., Koerfer, R., Holtz, J., & Zerkowski, H.-R. (1999). 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. Circulation, 100(suppl_2).

Authors 10

Babett Bartling (first)
Hendrik Milting (additional)
Heike Schumann (additional)
Dorothea Darmer (additional)
Lativ Arusoglu (additional)
Michael Matthias Koerner (additional)
Aly El-Banayosy (additional)
Reiner Koerfer (additional)
Juergen Holtz (additional)
Hans-Reinhard Zerkowski (additional)

References 32 Referenced 13

McCarthy PM. Heartmate implantable left ventricular assist device: bridge to transplantation and future applications. Ann Thorac Surg. 1995;59:846–851. / Ann Thorac Surg (1995)
10.1016/0003-4975(94)91946-1
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Bartling B Schumann H Holtz J Grapow M Zerkowski H-R Darmer D. Effect of ACE inhibitors on the expression of Bcl-2 related genes in failing human left ventricular myocardium. Circulation. 1998;98(suppl I):I-75. Abstract.
10.1006/bbrc.1997.7555
10.4049/jimmunol.156.1.13
Reed JC. Mechanisms of Bcl-2 family proteins function and dysfunction in health and disease. Behring Inst Mitt. 1996;97:72–100. / Behring Inst Mitt (1996)
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Dates

Type	When
Created	4 years, 2 months ago (July 2, 2021, 8:39 p.m.)
Deposited	1 year, 3 months ago (May 13, 2024, 12:15 p.m.)
Indexed	3 months, 2 weeks ago (May 20, 2025, 10:34 a.m.)
Issued	25 years, 9 months ago (Nov. 9, 1999)
Published	25 years, 9 months ago (Nov. 9, 1999)
Published Print	25 years, 9 months ago (Nov. 9, 1999)

Funders 0

None

BibTeX

@article{Bartling_1999, title={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}, volume={100}, ISSN={1524-4539}, url={http://dx.doi.org/10.1161/circ.100.suppl_2.ii-216}, DOI={10.1161/circ.100.suppl_2.ii-216}, number={suppl_2}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Bartling, Babett and Milting, Hendrik and Schumann, Heike and Darmer, Dorothea and Arusoglu, Lativ and Koerner, Michael Matthias and El-Banayosy, Aly and Koerfer, Reiner and Holtz, Juergen and Zerkowski, Hans-Reinhard}, year={1999}, month=nov }

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      }
    }
  ]
}