title: Pressure mediated hypertrophy and mechanical stretch up-regulate expression of the long form of leptin receptor (ob-Rb) in rat cardiac myocytes.
abstract: BACKGROUND
  Hyperleptinemia is known to participate in cardiac hypertrophy and hypertension, but the relationship between pressure overload and leptin is poorly understood. We therefore examined the expression of leptin (ob) and the leptin receptor (ob-R) in the pressure-overloaded rat heart. We also examined gene expressions in culture cardiac myocytes to clarify which hypertension-related stimulus induces these genes.
  
  
  RESULTS
  Pressure overload was produced by ligation of the rat abdominal aorta, and ob and ob-R isoform mRNAs were measured using a real-time polymerase chain reaction (PCR). We also measured these gene expressions in neonatal rat cardiac myocytes treated with angiotensin II (ANGII), endothelin-1 (ET-1), or cyclic mechanical stretch. Leptin and the long form of the leptin receptor (ob-Rb) gene were significantly increased 4 weeks after banding, but expression of the short form of the leptin receptor (ob-Ra) was unchanged. ob-Rb protein expression was also detected by immunohistochemistry in hypertrophied cardiac myocytes after banding. Meanwhile, plasma leptin concentrations were not different between the control and banding groups. In cultured myocytes, ANGII and ET-1 increased only ob mRNA expression. However, mechanical stretch activated both ob and ob-Rb mRNA expression in a time-dependent manner, but ob-Ra mRNA was unchanged by any stress.
  
  
  CONCLUSIONS
  We first demonstrated that both pressure mediated hypertrophy and mechanical stretch up-regulate ob-Rb gene expression in heart and cardiac myocytes, which are thought to be important for leptin action in cardiac myocytes. These results suggest a new local mechanism by which leptin affects cardiac remodeling in pressure-overloaded hearts.
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Showa-machi, Maebashi, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsui
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Chie
authors.initials: C
authors.lastname: Tanaka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sunaga
authors.forename: Norimichi
authors.initials: N
authors.lastname: Koitabashi
authors.forename: Takako
authors.initials: T
authors.lastname: Takizawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Arai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D006984:Hypertrophy; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D011312:Pressure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D020738:Leptin; D020033:Protein Isoforms; D012333:RNA, Messenger; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D000804:Angiotensin II