title: Insulin-like growth factor-binding protein-3 induces fetalization in neonatal rat cardiomyocytes.
abstract: We employed cDNA microarrays representing 4000 distinct sequences to profile changes in gene expression in a rodent model of heart disease, namely, progression to heart failure after myocardial infarction. Differential gene expression in the left ventricle was examined at 4-week intervals over a 12-week period after coronary artery ligation in rats. Over this time course, insulin-like growth factor-binding protein-3 (IGFBP-3) was found to have a greater expression than in nondiseased tissues. We then employed quantitative real-time PCR to analyze gene expression in neonatal rat cardiac myocytes that had been treated with recombinantly expressed IGFBP-3 to examine a number of transcriptional responses designed to reflect the heart failure phenotype. The IGFBP-3 protein was shown to induce transcription of atrial natriuretic factor (ANF) and beta-myosin heavy chain (B-MHC). Analysis of conditioned media taken from IGFBP-3-treated cardiac myocyte cultures demonstrated an increase in ANF protein as well as in protein synthesis, as determined by metabolic incorporation of a radiolabeled amino acid. However, transcriptional changes of troponin-1, endothelin-1, or angiotensin-II by IGFBP-3 were not observed.
authors.affiliation: Scios Inc., 820 W. Maude Ave., Sunnyvale, CA 94086, USA.
authors.forename: M
authors.initials: M
authors.lastname: Henson
authors.forename: D
authors.initials: D
authors.lastname: Damm
authors.forename: A
authors.initials: A
authors.lastname: Lam
authors.forename: L J
authors.initials: LJ
authors.lastname: Garrard
authors.forename: T
authors.initials: T
authors.lastname: White
authors.forename: J A
authors.initials: JA
authors.lastname: Abraham
authors.forename: G F
authors.initials: GF
authors.lastname: Schreiner
authors.forename: L W
authors.initials: LW
authors.lastname: Stanton
authors.forename: A H
authors.initials: AH
authors.lastname: Joly
mesh_terms: D000804:Angiotensin II / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D019332:Endothelin-1 / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000196:embryology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009203:Myocardial Infarction / Q000235:genetics*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D019210:Troponin I / Q000235:genetics
chemical_list: D019332:Endothelin-1; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019210:Troponin I; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D009320:Atrial Natriuretic Factor; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains