Adverse Effects on β-Adrenergic Receptor Coupling

Ischemic Postconditioning Failed to Preserve Long-Term Cardiac Function

Rolf Schreckenberg, Péter Bencsik, Martin Weber, Yaser Abdallah, C. Csonka, Kamilla Gömöri, Krisztina Kiss, János Pálóczi, Judit Pipis, Márta Sárközy, Péter Ferdinandy, Rainer Schulz, Klaus Dieter Schlüter

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND: Ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) are currently among the most efficient strategies protecting the heart against ischemia/reperfusion injury. However, the effect of IPC and IPoC on functional recovery following ischemia/reperfusion is less clear, particularly with regard to the specific receptor-mediated signaling of the postischemic heart. The current article examines the effect of IPC or IPoC on the regulation and coupling of β-adrenergic receptors and their effects on postischemic left ventricular function. METHODS AND RESULTS: The β-adrenergic signal transduction was analyzed in 3-month-old Wistar rats for each of the intervention strategies (Sham, ischemia/reperfusion, IPC, IPoC) immediately and 7 days after myocardial infarction. Directly after the infarction a cardioprotective potential was demonstrated for both IPC and IPoC: the infarct size was reduced, apoptosis and production of reactive oxygen species were lowered, and the myocardial tissue was preserved. Seven days after myocardial ischemia, only IPC hearts showed significant functional improvement. Along with a deterioration in fractional shortening, IPoC hearts no longer responded adequately to β-adrenergic stimulation. The stabilization of β-adrenergic receptor kinase-2 via increased phosphorylation of Mdm2 (an E3-ubiquitin ligase) was responsible for desensitization of β-adrenergic receptors and identified as a characteristic specific to IPoC hearts. CONCLUSIONS: Immediately after myocardial infarction, rapid and transient activation of β-adrenergic receptor kinase-2 may be an appropriate means to protect the injured heart from excessive stress. In the long term, however, induction and stabilization of β-adrenergic receptor kinase-2, with the resultant loss of positive inotropic function, leads to the functional picture of heart failure.

Original languageEnglish
JournalJournal of the American Heart Association
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 22 2017

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Ischemic Postconditioning
Ischemic Preconditioning
Adrenergic Receptors
Phosphotransferases
Adrenergic Agents
Reperfusion
Ischemia
Myocardial Infarction
Ubiquitin-Protein Ligases
Reperfusion Injury
Left Ventricular Function
Infarction
Myocardial Ischemia
Wistar Rats
Reactive Oxygen Species
Signal Transduction
Heart Failure
Phosphorylation
Apoptosis

Keywords

  • cardiac remodeling
  • ischemic postconditioning
  • ischemic preconditioning
  • myocardial infarction
  • β‐adrenergic receptor
  • β‐adrenergic receptor kinase‐2

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Adverse Effects on β-Adrenergic Receptor Coupling : Ischemic Postconditioning Failed to Preserve Long-Term Cardiac Function. / Schreckenberg, Rolf; Bencsik, Péter; Weber, Martin; Abdallah, Yaser; Csonka, C.; Gömöri, Kamilla; Kiss, Krisztina; Pálóczi, János; Pipis, Judit; Sárközy, Márta; Ferdinandy, Péter; Schulz, Rainer; Schlüter, Klaus Dieter.

In: Journal of the American Heart Association, Vol. 6, No. 12, 22.12.2017.

Research output: Contribution to journalArticle

Schreckenberg, R, Bencsik, P, Weber, M, Abdallah, Y, Csonka, C, Gömöri, K, Kiss, K, Pálóczi, J, Pipis, J, Sárközy, M, Ferdinandy, P, Schulz, R & Schlüter, KD 2017, 'Adverse Effects on β-Adrenergic Receptor Coupling: Ischemic Postconditioning Failed to Preserve Long-Term Cardiac Function', Journal of the American Heart Association, vol. 6, no. 12. https://doi.org/10.1161/JAHA.117.006809
Schreckenberg, Rolf ; Bencsik, Péter ; Weber, Martin ; Abdallah, Yaser ; Csonka, C. ; Gömöri, Kamilla ; Kiss, Krisztina ; Pálóczi, János ; Pipis, Judit ; Sárközy, Márta ; Ferdinandy, Péter ; Schulz, Rainer ; Schlüter, Klaus Dieter. / Adverse Effects on β-Adrenergic Receptor Coupling : Ischemic Postconditioning Failed to Preserve Long-Term Cardiac Function. In: Journal of the American Heart Association. 2017 ; Vol. 6, No. 12.
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AU - Weber, Martin

AU - Abdallah, Yaser

AU - Csonka, C.

AU - Gömöri, Kamilla

AU - Kiss, Krisztina

AU - Pálóczi, János

AU - Pipis, Judit

AU - Sárközy, Márta

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AU - Schlüter, Klaus Dieter

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