Small molecule cardiogenol C upregulates cardiac markers and induces cardiac functional properties in lineage-committed progenitor cells

Cell Physiol Biochem. 2014;33(1):205-21. doi: 10.1159/000356663. Epub 2014 Jan 24.

Abstract

Background/aims: Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules.

Methods: Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays.

Results: Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies.

Conclusion: CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Animals
  • Atrial Natriuretic Factor / metabolism
  • Biomarkers / metabolism*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Lineage / drug effects*
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / metabolism
  • Humans
  • Ion Channel Gating / drug effects
  • Mice
  • Myoblasts, Skeletal / drug effects
  • Myoblasts, Skeletal / metabolism
  • Myocardium / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Rats
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Stem Cells
  • Transcription Factors / metabolism
  • Up-Regulation / drug effects*

Substances

  • Aniline Compounds
  • Biomarkers
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • NKX2-5 protein, human
  • Pyrimidines
  • Small Molecule Libraries
  • Transcription Factors
  • cardiogenol C
  • Atrial Natriuretic Factor