Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction
Thomas E. Sharp III, Hajime Kubo, Remus M. Berretta, Timothy Starosta, Markus Wallner, Giana J. Schena, Alexander R. Hobby, Daohai Yu, Danielle M. Trappanese, Jon C. George, Jeffery D. Molkentin and Steven R. Houser
RBX Reduces PKCα Phosphorylation at T638 and Does Not Directly Alter PKA-Dependent Signaling
(A) Western blot for total PKCα and phosphorylation at threonine 638 (T638) after MI ± RBX. T638 phosphorylation was reduced in the presences of RBX (B) Correlation of T638 phosphorylation and echocardiographic volumetric analysis. Increased phosphorylation was positively correlated to increases in LVEDV and LVESV at 3 months PMI, and reduced LVEF. (C) Western blot for total phospholamban (PLN) and phosphorylation sites, serine 16 (S16) and threonine 17 (T17). RBX had no effect on the S16 or T17 phosphorylation. †p ≤ 0.05 versus 3 months PMI. Abbreviations as in Figures 1, 2, 4, and 5.