Ca²+-regulatory proteins in cardiomyocytes from the right ventricle in children with congenital heart disease

J Transl Med. 2012 Apr 2;10:67. doi: 10.1186/1479-5876-10-67.


Background: Hypoxia and hypertrophy are the most frequent pathophysiological consequence of congenital heart disease (CHD) which can induce the alteration of Ca2+-regulatory proteins and inhibit cardiac contractility. Few studies have been performed to examine Ca2+-regulatory proteins in human cardiomyocytes from the hypertrophic right ventricle with or without hypoxia.

Methods: Right ventricle tissues were collected from children with tetralogy of Fallot [n = 25, hypoxia and hypertrophy group (HH group)], pulmonary stenosis [n = 25, hypertrophy group (H group)], or small isolated ventricular septal defect [n = 25, control group (C group)] during open-heart surgery. Paraffin sections of tissues were stained with 3,3'-dioctadecyloxacarbocyanine perchlorate to measure cardiomyocyte size. Expression levels of Ca2+-regulatory proteins [sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), ryanodine receptor (RyR2), sodiumcalcium exchanger (NCX), sarcolipin (SLN) and phospholamban (PLN)] were analysed by means of real-time PCR, western blot, or immunofluorescence. Additionally, phosphorylation level of RyR and PLN and activity of protein phosphatase (PP1) were evaluated using western blot.

Results: Mild cardiomyocyte hypertrophy of the right ventricle in H and HH groups was confirmed by comparing cardiomyocyte size. A significant reduction of SERCA2a in mRNA (P<0.01) was observed in the HH group compared with the C group. The level of Ser16-phosphorylated PLN was down-regulated (P<0.01) and PP1 was increased (P<0.01) in the HH group compared to that in the C group.

Conclusions: The decreased SERCA2a mRNA may be a biomarker of the pathological process in the early stage of cyanotic CHD with the hypertrophic right ventricle. A combination of hypoxia and hypertrophy can induce the adverse effect of PLN-Ser16 dephosphorylation. Increased PP1 could result in the decreased PLN-Ser16 and inhibition of PP1 is a potential therapeutic target for heart dysfunction in pediatrics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Calcium / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Size
  • Child, Preschool
  • Demography
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Heart Defects, Congenital / enzymology
  • Heart Defects, Congenital / metabolism*
  • Heart Defects, Congenital / pathology
  • Heart Ventricles / enzymology
  • Heart Ventricles / metabolism*
  • Heart Ventricles / pathology
  • Humans
  • Male
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology*
  • Phosphorylation
  • Protein Phosphatase 1 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction


  • Calcium-Binding Proteins
  • RNA, Messenger
  • Protein Phosphatase 1
  • Calcium