title: Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocyte interactions during hypertrophy of rat cardiac myocytes in vitro.
abstract: BACKGROUND
  The mechanism responsible for cardiac hypertrophy is currently conceptualized as having 2 components, mediated by cardiac myocytes and nonmyocytes, respectively. The interaction between myocytes and nonmyocytes via growth factors and/or cytokines plays an important role in the development of cardiac hypertrophy. We found that cardiac myocytes showed hypertrophic changes when cocultured with cardiac nonmyocytes. Cardiotrophin-1 (CT-1), a new member of the interleukin-6 family of cytokines, was identified by its ability to induce hypertrophic response in cardiac myocytes. In this study, we used the in vitro coculture system to examine how CT-1 is involved in the interaction between cardiac myocytes and nonmyocytes during the hypertrophy process.
  
  
  RESULTS
  RNase protection assay revealed that CT-1 mRNA levels were 3. 5 times higher in cultured cardiac nonmyocytes than in cultured cardiac myocytes. We developed anti-CT-1 antibodies and found that they significantly inhibited the increased atrial and brain natriuretic peptide secretion and protein synthesis characteristic of hypertrophic changes of myocytes in the coculture. In addition, non-myocyte-conditioned medium rapidly elicited tyrosine phosphorylation of STAT3 and induced an increase in natriuretic peptide secretion and protein synthesis in cultured cardiac myocytes; these effects were partially suppressed by anti-CT-1 antibodies. Finally, the hypertrophic effects of CT-1 and endothelin-1, which we had previously implicated in the hypertrophic activity in the coculture, were additive in cardiac myocytes.
  
  
  CONCLUSIONS
  These results show that CT-1 secreted from cardiac nonmyocytes is significantly involved in the hypertrophic changes of cardiac myocytes in the coculture and suggest that CT-1 is an important local regulator in the process of cardiac hypertrophy.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kuwahara
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: E
authors.initials: E
authors.lastname: Ogawa
authors.forename: Y
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: I
authors.initials: I
authors.lastname: Hamanaka
authors.forename: S
authors.initials: S
authors.lastname: Kamitani
authors.forename: N
authors.initials: N
authors.lastname: Kajiyama
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: O
authors.initials: O
authors.lastname: Nakagawa
authors.forename: I
authors.initials: I
authors.lastname: Masuda
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D006332:Cardiomegaly / Q000473:pathology* / Q000503:physiopathology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
chemical_list: D000906:Antibodies; D016207:Cytokines; D019332:Endothelin-1; D012333:RNA, Messenger; C092073:cardiotrophin 1