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

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

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  • 1State Key Laboratory of Cardiovascular Medicine, Cardiovascular Institute & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Abstract

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.

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