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Title: Embryonic gene expression in nonoverloaded ventricles of hereditary hypertrophic cardiomyopathic hamsters
Authors: DiNardo, P
Fiaccavento, R
Natali, A
Minieri, M
Sampaolesi, Maurilio
Fusco, A
Janmot, C
Cuda, G
Carbone, A
Rogliani, P
Peruzzi, G #
Issue Date: Nov-1997
Series Title: Laboratory Investigation vol:77 issue:5 pages:489-502
Abstract: Current information regarding the molecular and biochemical mechanisms of myocardial hypertrophy, as obtained from isolated cardiomyocytes and/or healthy animals with aortic banding, does not permit dissection of the hierarchical relationship among different steps and triggers of the pathogenic process in vivo. The aim of the present study was to depict the temporal relationship among myocardial structural and functional characteristics, the embryonic gene program, and transforming growth factor (TGF)beta 1 expression in euthyroid hereditary hypertrophic cardiomyopathic hamsters (CMPH). This investigation was performed using Western and Northern blot and in situ hybridization techniques. The results show that in CMPH, the severity of the hemodynamic overload is not related to any modification in structural myocardial characteristics (cardiac mass, cardiomyocyte dimensions, total RNA, and protein content), whereas an early activation of the embryonic gene program occurs in not yet overloaded 90-day-old CMPH (left ventricular end diastolic pressure < 15 mm Hg). In these animals, a 30% to 90% decrease in the or myosin heavy chain (alpha MHC) relative content was found in ventricles, whereas beta MHC increased 5-fold. In addition, the oc skeletal actin expression was enhanced 2-fold versus age-matched controls. No modifications were observed in myosin function evaluated by in vitro motility assay, whereas the administration of L-thyroxine (100 mu g/kg intraperitoneally daily) to CMPH was able to reinduce the ventricular expression of the alpha MHC isoform (5-fold increase). Conversely, no changes were found in Lu cardiac actin and myosin light chain 2 (MLC2) expression. A close temporal relationship occurred in CMPH ventricles between the re-expression of the embryonic gene program and a 3-fold enhancement of the expression of TGF beta 1. These results indicate that the CMPH provides a useful model for investigating the expression of embryonic genes in hypertrophic ventricles in the absence of mechanical and hormonal stimuli, and that TGF beta 1 is involved in regulating in vivo the ''embryonic step'' of myocardial hypertrophy. Furthermore, the study offers new insights into the pathophysiologic mechanisms leading to heart failure.
ISSN: 0023-6837
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdepartemental Stem Cell Institute (-)
# (joint) last author

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