Figure 7

Schematic representation of the blocking effect of sorafenib on development of left ventricle hypertrophy (LVH) induced by aortic banding. Mechanical stretch induced by pressure overload results in over-expression of growth factors, PDGF-BB and TGFβ1 in myocardium [5]. The original finding of this study shows sorafenib to inhibit the up-regulation of these growth factors following AB. Phosphorylation and hence activation of PDGFβR and TGFβ1R is known to activate the downstream signaling pathway of c-Raf/ERK1/2 [10]. Sorafenib is reported to block phosphorylation and activation of PDGFβR and c-Raf in cancer studies [23]. By blocking the c-Raf/ERK1/2 cascade, sorafenib down-regulates the expression of pro-proliferative (c-myc, c-fos) and pro-hypertrophic (GATA4) transcription factors as well. One of the pro-hypertrophic effector mechanisms regulated by GATA4 is ANP [14] which is in turn suppressed by sorafenib treatment. The sum of the inhibitory effects of sorafenib ends at the suppression of cardiomyocyte hypertrophy as well as of interstitial collagen deposition, the two main components of LVH. Blocking effect of sorafenib on expression of growth factor as demonstrated in this study. Blocking effect of sorafenib previously reported by Wilhelm et al. [23].