Changes in contractile protein expression are linked to ventricular stiffness in infants with pulmonary hypertension or right ventricular hypertrophy due to congenital heart disease
Date
2017-11-18
Authors
Bond, Andrew R
Iacobazzi, Dominga
Abdul-Ghani, Safa
Ghorbel, Mohammed
Heesom, Kate
Wilson, Mariangela
Gillett, Christopher
George, Sarah J
Caputo, Massimo
Suleiman, Saadeh
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Abstract
Background The right ventricle (RV) is not designed
to sustain high pressure leading to failure. There are
no current medications to help RV contraction, so
further information is required on adaption of the RV
to such hypertension.
Methods The Right Ventricle in Children (RVENCH)
study assessed infants with congenital heart disease
undergoing cardiac surgery with hypertensive RV.
Clinical and echocardiographic data were recorded,
and samples of RV were taken from matched infants,
analysed for proteomics and compared between
pathologies and with clinical and echocardiographic
outcome data.
Results Those with tetralogy of Fallot (TOF)
were significantly more cyanosed than those with
ventricular septal defect (median oxygen saturation
83% vs 98%, P=0.0038), had significantly stiffer
RV (tricuspid E wave/A wave ratio 1.95 vs 0.84,
P=0.009) and had most had restrictive physiology.
Gene ontology in TOF, with enrichment analysis,
demonstrated significant increase in proteins of
contractile mechanisms and those of calmodulin,
actin binding and others associated with contractility
than inventricular septal defect. Structural proteins
were also found to be higher in association with
sarcomeric function: Z-disc, M-Band and thin-filament
proteins. Remaining proteins associated with actin
binding, calcium signalling and myocyte cytoskeletal
development. Phosphopeptide enrichment led to
higher levels of calcium signalling proteins in TOF.
Conclusion This is the first demonstration that
those with an RV, which is stiff and hypertensive
in TOF, have a range of altered proteins, often in
calcium signalling pathways. Information about these
alterations might guide treatment options both in
terms of individualised therapy or inotropic support
for the Right ventricle when hypertensive due to
pulmoanry hypertension or congenital heart disease.
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Citation
Bond AR, Iacobazzi D, Abdul-Ghani S, et al. Changes in contractile protein expression are linked to ventricular stiffness in infants with pulmonary hypertension or right ventricular hypertrophy due to congenital heart disease.