Insulin-like growth factor-binding protein-3 induces fetalization in neonatal rat cardiomyocytes

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-l, endothelin-l, or angiotensin-n: by IGFBP-3 were not observed.