Exercise rescued chronic kidney disease by attenuating cardiac hypertrophy through the cardiotrophin-1 → LIFR/gp 130 → JAK/STAT3 pathway

Kuan Chou Chen, Chiu Lan Hsieh, Chiung Chi Peng, Robert Y. Peng

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background: Chronic kidney disease (CKD) is usually associated with cardiac apoptosis and/or cardiac hypertrophy. We hypothesized that exercise can reduce the CKD-induced cardiac damage. Methods and results: The doxorubicin-induced CKD (DRCKD) model was used in rats to compare two exercise models: 60-min running and 60-min swimming. Results indicated that in healthy normal groups, the signals cardiotrophin- 1 (CT-1), interleukin 6 (IL-6), leukaemia inhibitory factor receptor (LIFR), and gp130 were upregulated and janus kinase (JAK) and signal transducer and activation of transcription (STAT) were downregulated by both exercises. In contrast, all signals were highly upregulated in CKD. After exercise training, all signals (CT-1, IL-6, LIFR, gp130, and STAT) were downregulated, with JAK being only slightly upregulated in the running group but not in the swimming group. The myocyte death pathway (CT-1/IL-6→LIFR/ gp130→PI3K→Akt→Bad) was excluded due to no change found for Bad. Nitric oxide (NO; normal, 15.63± 0.86 mmol/l) was significantly suppressed in CKD rats (2.95±;0.32 mmol/l), and both running and swimming training highly upregulated the NO level to 30.33± 1.03 mmol/l and 27.82± 2.47 mmol/l in normal subjects and 24.0± 3.2 mmol/l and 22.69± 3.79 mmol/l in the DRCKD rats, respectively. The endothelial progenic cells CD34 were significantly suppressed in DRCKD rats, which were not rescued significantly by exercise. In contrast, the CD 34 cells were only slightly suppressed in the healthy subjects by exercise. Conclusion: Both exercise regimens were beneficial by rescuing cardiac function in CKD victims. Its action mechanism was by way of inhibiting myocyte death and rescuing cardiac hypertrophy.

Original languageEnglish
Pages (from-to)507-520
Number of pages14
JournalEuropean Journal of Preventive Cardiology
Issue number4
Publication statusPublished - Apr 2014


  • Cardiac hypertrophy
  • chronic kidney disease (CKD)
  • doxorubicin

ASJC Scopus subject areas

  • Epidemiology
  • Cardiology and Cardiovascular Medicine


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