Desmin gene expression in cardiac myocytes is responsive to
contractile activity and stretch: relevance to idiopathic
cardiomyopathy and pressure-induced hypertrophy.
Watson, Peter A., Ross Hannan, Lois L. Carl, and Kathryn E. Giger.
Weis Center for Research, Geisinger Clinic, 100 North Academy
Avenue, Danville, PA 17822-2615
APStracts 2:0362C, 1995.
Experiments were performed to assess the ability of mechanical
stimuli, experienced by ventricular cardiac myocytes during the
progression of hypertrophic and dilated pathology, to increase the
expression of desmin in cultured neonatal rat cardiac myocytes.
Results indicate that both contractile activity and load due to
passive stretch increase desmin content in neonatal rat cardiac
myocytes through increased desmin gene transcription. Western blot
analysis demonstrated that contraction induced a selective increase
in desmin protein content in neonatal rat cardiac myocytes above
increases observed in the content of total cellular protein. Northern
blot analysis indicated that desmin mRNA content increased in
response to contraction as well as alpha-adrenergic stimulation.
Desmin mRNA content also increased in cultured neonatal myocytes in
response to stretch. Angiotensin II (AII) treatment of contracting
neonatal cardiac myocytes further increased desmin mRNA content,
while similar treatment in arrested neonatal cardiac myocytes failed
to increase desmin mRNA. This contraction-dependent responsiveness to
AII is not a function of increases in the density or relative subtype
composition of AII-receptors. Treatment of contracting neonatal rat
cardiac myocytes with actinomycin-D prevented increases in desmin
mRNA content, suggesting regulation of transcription of the desmin
gene by contraction. Nuclear run-on experiments indicate that
contraction increases transcription of the desmin gene in cardiac
myocytes. These results are consistent with the modulation of desmin
gene expression secondarily to changes in the mechanical environment
which occur in cardiac tissue undergoing dilation or hypertrophy.
Received 27 June 1995; accepted in final form 27 September 1995.
APS Manuscript Number C380-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95