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Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity
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Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity

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

Kyoji Urayama1, Célia Guilini, Nadia Messaddeq

  • 1UMR 7175/CNRS/Universite Strasbourg I, Ecole Supérieure de Biotechnologie de Strasbourg, Bld. Sébastien Brandt BP. 10413, F-67412 Illkirch, France.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|April 20, 2007
PubMed

Insights

Prokineticin receptor-1 (PKR1) signaling promotes heart repair after myocardial infarction by enhancing blood vessel formation and protecting heart cells. PKR1 gene transfer reduced mortality and improved heart function in a mouse model.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Regenerative Medicine

Background:

  • Prokineticins are angiogenic factors acting through G protein-coupled receptors.
  • Prokineticin receptor-1 (PKR1/GPR73) signaling's role in myocardial infarction is unknown.
  • Prokineticin-2 and PKR1 are expressed in adult mouse heart and cardiac cells.

Purpose of the Study:

  • Investigate the role of prokineticin-2 and PKR1 in cardiac cell function.
  • Determine if PKR1 gene transfer can protect the heart from myocardial infarction.

Main Methods:

  • In vitro studies using cultured cardiac endothelial cells and cardiomyocytes (H9c2 cells).
  • Overexpression and siRNA knockdown of PKR1.
  • Intramyocardial gene transfer of PKR1 in a mouse model of myocardial infarction.
  • Analysis of human end-stage failing heart samples.

Main Results:

  • Prokineticin-2 and PKR1 overexpression promoted vessel-like formation in endothelial cells and protected cardiomyocytes from oxidative stress via Akt activation.
  • PKR1 knockdown reversed these pro-survival and pro-angiogenic effects.
  • Intramyocardial PKR1 gene transfer reduced mortality, preserved left ventricular function, and promoted neovascularization post-myocardial infarction.
  • Reduced PKR1 and prokineticin-2 levels were observed in human failing hearts.

Conclusions:

  • PKR1 signaling is crucial for cardiomyocyte survival and angiogenesis in the context of myocardial infarction.
  • PKR1 gene transfer demonstrates therapeutic potential for limiting myocardial injury.
  • PKR1 represents a novel therapeutic target for ischemic heart disease.

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