Time dependent changes in cytoplasmic proteins of the right ventricle during prolonged pressure overload.
In many forms of congenital heart disease, the right ventricle (RV) is subject to abnormal loading conditions resulting in RV hypertrophy and remodeling. We determined the alterations in RV cytoplasmic proteomic phenotype that occur during prolonged periods of RV pressure overload. We performed a differential proteomic profiling study on RV hypertrophy using an animal model of various durations of pulmonary artery banding (PAB) in parallel with hemodynamic characterization. This hemodynamic evaluation showed that after 6, 12 and 20 weeks of PAB, the RV is in a compensated state of hypertrophy. Overall, the majority of protein changes were metabolism related indicating a shift towards the glycolytic pathway at the expense of beta-oxidation in the RV of the PAB animals. The changes in proteins related to the glycolytic pathway, exemplified by enolase and creatine kinase B-chain, tended to precede changes in beta-oxidation. In parallel, increases in stress chaperones, exemplified by several phosphorylated HSP-27 species, are present from the 6 week time point, whereas increases in antioxidant proteins, exemplified by peroxiredoxin 2 and 6, appear to be restricted to the 12 week time point. The p38 MAPK signal transduction pathway appears not to be activated. Observed protein changes are likely part of a protective mechanism against the development of RV failure.
Faber
Matthijs J
MJ
Erasmus MC-Sophia, Department of Pediatrics, Division of Pediatric Cardiology, Room Sp-2429, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.
Dalinghaus
Michiel
M
Lankhuizen
Inge M
IM
Bezstarosti
Karel
K
Verhoeven
Adrie J M
AJ
Duncker
Dirk J
DJ
Helbing
Willem A
WA
Lamers
Jos M J
JM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight; D002302:Cardiac Output; D003593:Cytoplasm / Q000378:metabolism*; D019281:Dimerization; D006339:Heart Rate; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006984:Hypertrophy; D008297:Male; D009929:Organ Size; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D017725:Ventricular Pressure; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D006360:Heat-Shock Proteins; D020543:Proteome; D048051:p38 Mitogen-Activated Protein Kinases; D010751:Phosphopyruvate Hydratase