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Eur Heart J. 2014 Oct 14;35(39):2722-31. doi: 10.1093/eurheartj/ehs338. Epub 2012 Oct 25.

The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation.

Author information

  • 1Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, UK.
  • 2Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, UK Laboratory of Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Viale Europa, Catanzaro 88100, Italy.
  • 3Stem Cell and Regenerative Biology Unit (BioStem), Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool L3 3AF, UK Laboratory of Molecular and Cellular Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, Viale Europa, Catanzaro 88100, Italy g.m.ellison@ljmu.ac.uk torella@ljmu.ac.uk.

Abstract

AIMS:

It is a dogma of cardiovascular pathophysiology that the increased cardiac mass in response to increased workload is produced by the hypertrophy of the pre-existing myocytes. The role, if any, of adult-resident endogenous cardiac stem/progenitor cells (eCSCs) and new cardiomyocyte formation in physiological cardiac remodelling remains unexplored.

METHODS AND RESULTS:

In response to regular, intensity-controlled exercise training, adult rats respond with hypertrophy of the pre-existing myocytes. In addition, a significant number (∼7%) of smaller newly formed BrdU-positive cardiomyocytes are produced by the exercised animals. Capillary density significantly increased in exercised animals, balancing cardiomyogenesis with neo-angiogenesis. c-kit(pos) eCSCs increased their number and activated state in exercising vs. sedentary animals. c-kit(pos) eCSCs in exercised hearts showed an increased expression of transcription factors, indicative of their commitment to either the cardiomyocyte (Nkx2.5(pos)) or capillary (Ets-1(pos)) lineages. These adaptations were dependent on exercise duration and intensity. Insulin-like growth factor-1, transforming growth factor-β1, neuregulin-1, bone morphogenetic protein-10, and periostin were significantly up-regulated in cardiomyocytes of exercised vs. sedentary animals. These factors differentially stimulated c-kit(pos) eCSC proliferation and commitment in vitro, pointing to a similar role in vivo.

CONCLUSION:

Intensity-controlled exercise training initiates myocardial remodelling through increased cardiomyocyte growth factor expression leading to cardiomyocyte hypertrophy and to activation and ensuing differentiation of c-kit(pos) eCSCs. This leads to the generation of new myocardial cells. These findings highlight the endogenous regenerative capacity of the adult heart, represented by the eCSCs, and the fact that the physiological cardiac adaptation to exercise stress is a combination of cardiomyocyte hypertrophy and hyperplasia (cardiomyocytes and capillaries).

© The Author 2012. Published by Oxford University Press on behalf of European Society of Cardiology.

KEYWORDS:

Cardiac stem cells; Cardiomyogenesis; Exercise; Growth factors; Myocyte hyperplasia; Physiological remodelling

PMID:
23100284
[PubMed - in process]
PMCID:
PMC4196078
Free PMC Article
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