Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart

Ábel Perjés, Teemu Kilpiö, Johanna Ulvila, Johanna Magga, Tarja Alakoski, Zoltán Szabó, Laura Vainio, Eveliina Halmetoja, Olli Vuolteenaho, Ulla Petäjä-Repo, István Szokodi, Risto Kerkelä

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30 Citations (Scopus)

Abstract

The G protein-coupled apelin receptor regulates important processes of the cardiovascular homeostasis, including cardiac development, cardiac contractility, and vascular tone. Most recently, a novel endogenous peptide ligand for the apelin receptor was identified in zebrafish, and it was named apela/elabela/toddler. The peptide was originally considered as an exclusively embryonic regulator, and so far its function in the adult organism remains elusive. We show here that apela is predominantly expressed in the non-cardiomyocyte fraction in the adult rodent heart. We also provide evidence that apela binds to apelin receptors in the heart. Using isolated adult rat hearts, we demonstrate, that just like the fellow receptor agonist apelin, apela increases cardiac contractility and induces coronary vasodilation already in the nanomolar level. The inotropic effect, as revealed by Western blot analysis, is accompanied by a significant increase in extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Pharmacological inhibition of ERK1/2 activation markedly attenuates the apela-induced inotropy. Analysis of samples from infarcted mouse hearts showed that expression of both apela and apelin receptor is induced in failing mouse hearts and correlate with left ventricular ejection fraction. Hence, we conclude that apela is present in the adult heart, is upregulated in post-infarction cardiac remodeling, and increases cardiac contractility in an ERK1/2-dependent manner.

Original languageEnglish
Article number2
Pages (from-to)1-12
Number of pages12
JournalBasic Research in Cardiology
Volume111
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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Keywords

  • Apela
  • Cardiovascular
  • Cell signaling
  • Contractility
  • Extracellular signal-regulated kinase (ERK)
  • G protein-coupled receptor (GPCR)
  • Heart failure
  • Myocardial infarction
  • Peptides

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Perjés, Á., Kilpiö, T., Ulvila, J., Magga, J., Alakoski, T., Szabó, Z., Vainio, L., Halmetoja, E., Vuolteenaho, O., Petäjä-Repo, U., Szokodi, I., & Kerkelä, R. (2016). Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart. Basic Research in Cardiology, 111(1), 1-12. [2]. https://doi.org/10.1007/s00395-015-0521-6