The prokineticin receptor-1 (GPR73) promotes cardiomyocyte survival and angiogenesis

Kyoji Urayama, Célia Guilini, Nadia Messaddeq, Kai Hu, Marja Steenman, Hitoshi Kurose, Georg Ert, Canan G. Nebigil

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Prokineticins are potent angiogenic factors that bind to two G protein-coupled receptors to initiate their biological effects. We hypothesize that prokineticin receptor-1 (PKR1/GPR73) signaling may contribute to cardiomyocyte survival or repair in myocardial infarction. Since we showed that prokineticin-2 and PKR1 are expressed in adult mouse heart and cardiac cells, we investigated the role of prokineticin-2 on capillary endothelial cell and cardiomyocyte function. In cultured cardiac endothelial cells, prokineticin-2 or overexpression of PKR1 induces vessel-like formation without increasing VEGF levels. In cardiomyocytes and H9c2 cells, prokineticin-2 or overexpressing PKR1 activates Akt to protect cardiomyocytes against oxidative stress. The survival and angiogenesis promoting effects of prokineticin-2 in cardiac cells were completely reversed by siRNA-PKR1, indicating PKR1 involvement. We thus, further investigated whether intramyocardial gene transfer of DNA encoding PKR1 may rescue the myocardium against myocardial infarction in mouse model. Transient PKR1 gene transfer after coronary ligation reduces mortality and preserves left ventricular function by promoting neovascularization and protecting cardiomyocytes without altering VEGF levels. In human end-stage failing heart samples, reduced PKR1 and prokineticin-2 transcripts and protein levels implicate a more important role for prokineticin-2/PKR1 signaling in heart. Our results suggest that PKR1 may represent a novel therapeutic target to limit myocardial injury following ischemic events.

Original languageEnglish
Pages (from-to)2980-2993
Number of pages14
JournalFASEB Journal
Volume21
Issue number11
DOIs
Publication statusPublished - Sep 2007

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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