PKC translocation and ERK1/2 activation in compensated right ventricular hypertrophy secondary to chronic emphysema.

Abstract

BackgroundRight ventricular hypertrophy (RVH) is an important complication of chronic lung disease. However, the signal transduction pathways involved as well as the physiological changes to the right ventricle have not been investigated. Emphysema was produced in male, Syrian Golden hamsters by intra-tracheal instillation of 250 IU/kg elastase (Emp, n = 17). Saline treated animals served as controls (Con, n = 15).ResultsNine months later, Emp hamsters had 75% greater lung volume, and evidence of RVH at the gross and myocyte level (RV:tibia length Emp 6.84 ± 1.18 vs. Con 5.14 ± 1.11 mg/mm; myocyte cross sectional area Emp 3737 vs. Con 2695 μm2), but not left ventricular hypertrophy. Serial echocardiographic analysis from baseline to nine months after induction of emphysema revealed increasing right ventricular internal dimension and decreased pulmonary artery acceleration time only in Emp hamsters. There was an increase in translocation of PKC βI and PKC ε from cytosolic to membranous cell fractions in RV of Emp hamsters. Phosphorylation of PKC ε was unchanged. Translocation of PKC α and βII were unchanged. Emp animals had a 22% increase in phospho-ERK 1/2, but no change in levels of total ERK 1/2 compared to Con.ConclusionThese data suggest that PKC βI, ε and ERK 1/2 may play a role in mediating compensated RVH secondary to emphysema and may have clinical relevance in the pathogenesis of RVH.

Selective Inhibition of Matrix Metalloproteinase Isozymes and in Vivo Protection against Emphysema by Substituted γ-Keto Carboxylic Acids

“…It is known that emphysema can be induced in hamsters by the intratracheal instillation of porcine pancreatic elastase (PPE) . This model was therefore used to examine the in vivo activity of our selective MMP-12 inhibitor 1j .…”