Proteomic changes in the pressure overloaded right ventricle after 6 weeks in young rats: Correlations with the degree of hypertrophy

被引:59
作者
Faber, MJ
Dalinghaus, M
Lankhuizen, IM
Bezstarosti, K
Dekkers, DHW
Duncker, DJ
Helbing, WA
Lamers, JMJ
机构
[1] Erasmus Univ, Med Ctr,Dept Biochem,Erasmus MC, Cardiovasc Res Sch COUER, Fac Med & Hlth Sci, NL-3000 DR Rotterdam, Netherlands
[2] Erasmus Univ, Cardiovasc Res Sch COUER, Erasmus MC Sophia Childrens Hosp, Dept Pediat,Div Pediat Cardiol,Ctr Med, NL-3000 DR Rotterdam, Netherlands
[3] Erasmus Univ, Ctr Med, Thoraxctr, Cardiovasc Res Sch COUER, NL-3000 DR Rotterdam, Netherlands
关键词
congenital heart disease; heart proteins; heat shock proteins; hypertrophy; post-translation modifications; right ventricle; two-dimensional differential gel electrophoresis;
D O I
10.1002/pmic.200401313
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Right ventricular (RV) hypertrophy is an important problem in congenital heart disease. We determined the alterations in phenotype that occur in the initial phase of RV hypertrophy and their possible correlations with the degree of hypertrophy. Therefore, we performed a differential proteomic profiling study on RV hypertrophy using an animal model of pulmonary artery banding (PAB) in parallel with hemodynamic characterization. The RV homogenates were subfractionated in myofilament and cytoplasmic proteins, which subsequently were separated by two-dimensional gel electrophoresis (2-DE), excised, and analyzed by mass spectrometry (MS). The cytoplasmic fraction showed expression changes in metabolic proteins, indicative of a shift from fatty acid to glucose as a substrate for energy supply. Up-regulation of three HSP-27s (1.9-, 1.7-, and 3.5-fold) indicated an altered stress response in RV hypertrophy. Detailed analysis by immunoblotting and MS showed that two of these HSP-27s were at least phosphorylated on Ser15. The myofilament fraction showed up-regulation of desmin and alpha-beta-crystallin (1.4-and 1.3-fold, respectively). This alteration in desmin was confirmed by 1-DE immunoblots. Certain differentially expressed proteins, such as HSP-27, showed a significant correlation with the RV weight to the body weight ratio in the PAB rats, suggesting an association with the degree of hypertrophy.
引用
收藏
页码:2519 / 2530
页数:12
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