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A heart-specific increase in cardiotrophin-1 gene expression precedes the establishment of ventricular hypertrophy in genetically hypertensive rats.

AbstractOBJECTIVE:
Cardiotrophin-1 is a cytokine, a novel member of the interleukin-6 superfamily, which is isolated from mouse embryoid bodies. It is known to bind a gp130/ leukemia inhibitory factor (LIF) receptor heterodimer and to induce myocyte hypertrophy. Accumulating evidence indicates that a gp130 signaling pathway is involved in cardiac development and ventricular hypertrophy.
METHODS:
In order to elucidate the pathophysiologic significance of cardiotrophin-1 in ventricular hypertrophy associated with hypertension, we examined the level of cardiotrophin-1 mRNA in the ventricle of spontaneously hypertensive rats/Izm stroke-prone (SHRSP/Izm) in neonates, and at 4-, 12- and 20-weeks of age by Northern blot analysis. We also examined the gene expression of LIF by Northern blot and reverse transcription-polymerase chain reaction analyses.
RESULTS:
No significant difference was observed in the level of cardiotrophin-1 mRNA in the ventricle between SHRSP/ Izm and Wistar-Kyoto/Izm (WKY/Izm) neonates. However, the level of cardiotrophin-1 mRNA in the ventricle was significantly augmented in 4-week-old SHRSP/Izm, which did not yet show overt ventricular hypertrophy, and its augmented expression lasted for the duration of the experimental period. The difference in the level of cardiotrophin-1 mRNA between the two strains was most prominent at the age of 4 weeks. This augmented expression of the cardiotrophin-1 gene was not related to the severity of left ventricular hypertrophy. The level of cardiotrophin-1 mRNA in other organs, including the kidney and lung, showed no significant change with aging and was not different between the two strains. After long-term treatment with lisinopril, levels of cardiotrophin-1 mRNA were not changed, although it morphologically prevented the development of left ventricular hypertrophy. LIF mRNA was not detected in any ventricles examined by Northern blot analysis.
CONCLUSIONS:
The present study demonstrates that the expression of cardiotrophin-1 mRNA is increased in the early stage of ventricular hypertrophy in SHRSP/Izm and it remains elevated after hypertrophy has been established. However, it is unlikely that cardiotrophin-1 plays a mechanistic role in the development and maintenance of left ventricular hypertrophy in SHRSP/Izm. The present study also suggests that cardiotrophin-1, but not LIF, is a possible candidate for natural ligand of a gp130 signaling pathway in the heart.
AuthorsM Ishikawa, Y Saito, Y Miyamoto, M Harada, K Kuwahara, E Ogawa, O Nakagawa, I Hamanaka, N Kajiyama, N Takahashi, I Masuda, T Hashimoto, O Sakai, T Hosoya, K Nakao
JournalJournal of hypertension (J Hypertens) Vol. 17 Issue 6 Pg. 807-16 (Jun 1999) ISSN: 0263-6352 [Print] England
PMID10459879 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Cytokines
  • DNA Primers
  • RNA, Messenger
  • cardiotrophin 1
  • Lisinopril
Topics
  • Angiotensin-Converting Enzyme Inhibitors (pharmacology)
  • Animals
  • Animals, Newborn
  • Biomarkers
  • Blotting, Northern
  • Cells, Cultured
  • Cytokines (biosynthesis, drug effects, genetics)
  • DNA Primers (chemistry)
  • Follow-Up Studies
  • Gene Expression
  • Heart Ventricles (drug effects, pathology)
  • Hypertension (complications, genetics, metabolism)
  • Hypertrophy, Left Ventricular (etiology, genetics)
  • Lisinopril (pharmacology)
  • Male
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction

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