Proteomic changes in the pressure overloaded right ventricle after 6 weeks in young rats: correlations with the degree of hypertrophy.
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-B-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.
Faber
Matthijs J
MJ
Department of Pediatrics, Division of Pediatric Cardiology, Erasmus MC-Sophia Children's Hospital, Cardiovascular Research School COEUR, Erasmus University Medical Center, Rotterdam, The Netherlands.
Dalinghaus
Michiel
M
Lankhuizen
Inge M
IM
Bezstarosti
Karel
K
Dekkers
Dick H W
DH
Duncker
Dirk J
DJ
Helbing
Willem A
WA
Lamers
Jos M J
JM
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D015180:Electrophoresis, Gel, Two-Dimensional; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D006439:Hemodynamics; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011312:Pressure; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology*; D016278:Ventricular Function, Right / Q000502:physiology*
D006360:Heat-Shock Proteins; D009124:Muscle Proteins