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Circ Res. 2010 Mar 19;106(5):891-901. doi: 10.1161/CIRCRESAHA.109.208629. Epub 2010 Jan 14.

Cardiac progenitor cell cycling stimulated by pim-1 kinase.

Author information

1
San Diego State Heart Institute, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182, USA.

Erratum in

  • Correction. [Endocr Pract. 2015]
  • Circ Res. 2015 Nov 6;117(11):e90. Avitable, Daniele [corrected to Avitabile, Daniele].

Abstract

RATIONALE:

Cardioprotective effects of Pim-1 kinase have been previously reported but the underlying mechanistic basis may involve a combination of cellular and molecular mechanisms that remain unresolved. The elucidation of the mechanistic basis for Pim-1 mediated cardioprotection provides important insights for designing therapeutic interventional strategies to treat heart disease.

OBJECTIVE:

Effects of cardiac-specific Pim-1 kinase expression on the cardiac progenitor cell (CPC) population were examined to determine whether Pim-1 mediates beneficial effects through augmenting CPC activity.

METHODS AND RESULTS:

Transgenic mice created with cardiac-specific Pim-1 overexpression (Pim-wt) exhibit enhanced Pim-1 expression in both cardiomyocytes and CPCs, both of which show increased proliferative activity assessed using 5-bromodeoxyuridine (BrdU), Ki-67, and c-Myc relative to nontransgenic controls. However, the total number of CPCs was not increased in the Pim-wt hearts during normal postnatal growth or after infarction challenge. These results suggest that Pim-1 overexpression leads to asymmetric division resulting in maintenance of the CPC population. Localization and quantitation of cell fate determinants Numb and alpha-adaptin by confocal microscopy were used to assess frequency of asymmetric division in the CPC population. Polarization of Numb in mitotic phospho-histone positive cells demonstrates asymmetric division in 65% of the CPC population in hearts of Pim-wt mice versus 26% in nontransgenic hearts after infarction challenge. Similarly, Pim-wt hearts had fewer cells with uniform alpha-adaptin staining indicative of symmetrically dividing CPCs, with 36% of the CPCs versus 73% in nontransgenic sections.

CONCLUSIONS:

These findings define a mechanistic basis for enhanced myocardial regeneration in transgenic mice overexpressing Pim-1 kinase.

PMID:
20075333
PMCID:
PMC3116713
DOI:
10.1161/CIRCRESAHA.109.208629
[Indexed for MEDLINE]
Free PMC Article

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