Reduction of c-kit positive cardiac stem cells in patients with atrial fibrillation

J Cardiol. 2017 May;69(5):712-718. doi: 10.1016/j.jjcc.2016.07.006. Epub 2016 Aug 4.

Abstract

Background: We aimed to determine expression patterns of cardiac stem cells in the left atrium (LA) tissue from patients with atrial fibrillation.

Methods: LA appendages were obtained during open-heart surgery and processed for explant cell culture and tissue analysis (n=319). The total number of grown cells and c-kit positive cells were analyzed by flow cytometry after 4 weeks of culture. The remaining tissue was used for Masson's trichrome staining to determine the area of the fibrosis.

Results: The diameter of the LA, as measured by echocardiography, was significantly larger in the AF group than in the sinus rhythm group. Reverse transcription polymerase chain reaction analysis revealed higher expression of collagen in the AF group and an increase in the expression of basic fibrosis growth factor and transforming growth factor-2 and -3. Masson's trichrome staining showed progression of fibrosis in the AF tissue. In addition, the expression of apoptosis-related genes were significantly higher in AF group. There was no difference in the expression of connexin-40 between groups, while the expression of connexin-43 was decreased and that of connexin-45 was increased in the AF group. The total numbers of grown cells as well as c-kit positive cells after 4 weeks of cardiac tissue culture were significantly lower in the AF group.

Conclusion: Progression of remodeling in LA tissue was observed in AF patients. The number of c-kit positive cells cultured from LA appendages was reduced in AF patients, suggesting impairments in self-renewal.

Keywords: Cardiac stem cells; Fibrosis; Gap junction; Remodeling; Self-renewal; c-kit.

MeSH terms

  • Aged
  • Atrial Appendage / pathology
  • Atrial Fibrillation / physiopathology*
  • Atrial Remodeling / physiology*
  • Cells, Cultured
  • Collagen / metabolism
  • Connexin 43 / metabolism
  • Connexins / metabolism
  • Echocardiography
  • Female
  • Fibroblast Growth Factors / metabolism
  • Heart Atria / diagnostic imaging
  • Humans
  • Male
  • Middle Aged
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transforming Growth Factors / metabolism

Substances

  • Connexin 43
  • Connexins
  • connexin 45
  • Fibroblast Growth Factors
  • Transforming Growth Factors
  • Collagen
  • Proto-Oncogene Proteins c-kit