Publication: Altered Cx43 expression during myocardial
adaptation to acute and chronic volume overloading
Authors
Formigli, L. ; Ibba-Manneschi, L. ; Perna, A.M. ; Pacini, A. ; Polidori, L. ; Nediani, C. ; Modesti, P.A. ; Nosi, Daniele ; Tani, A. ; Celli, A. ; Neri-Serneri, G.G. ; Quercioli, F. ; Zecchi-Orlandini, S.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Gap-junctions are specialized regions of
intercellular contacts allowing electrical impulse
propagation among adjacent cardiomyocytes.
Connexin43 (Cx43) is the predominant gap-junction
protein in the working ventricular myocardium and its
reduced expression has been extensively implicated in
the genesis of conduction abnormalities and re-entry
arrhythmia of chronically hypertrophied hearts. In
contrast, data on the role played by this protein during
cardiac remodeling and early phases of developing
hypertrophy are lacking. Therefore, in the present study,
we investigated this issue using an experimental model
of pig left ventricle (LV) volume overloading consisting
in the creation of an aorto-cava fistula. At scheduled
times (6, 24, 48, 96, 168 h, and 2, 3 months after
surgery) echocardiographic and haemodynamic
measurements were performed and myocardial biopsies
were taken for the morphological and biochemical
analyses. When faced with the increased load, pig
myocardium underwent an initial period (from 6 up to
48 h) of remarkable tissue remodeling consisting in the
occurrence of cardiomyocyte damage and apoptosis.
After that time, the tissue developed a hypertrophic
response that was associated with early dynamic changes
(up-regulation) in Cx43 protein expression, as
demonstrated by Western blot and confocal
immunofluorescence analyses. However, an initial
transient increase of this protein was also found after 6 h
from surgery. With the progression of LV hypertrophy
(from 168 hr up to 3 months), a reduction in the
myocardial Cx43 expression was, instead, observed. The
increased expression of Cx43 protein during acute
hypertrophic response was associated with a
corresponding increase in the levels of its specific
mRNA, as detected by RT-PCR. We concluded that upregulation
of Cx43 gap-junction protein could represent
an immediate compensatory response to support the new working conditions in the early stages of ventricular
overloading.
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