Effect of hepatocyte growth factor and angiotensin II on rat cardiomyocyte hypertrophy

Abstract

Angiotensin II (Ang II) plays an important role in cardiomyocyte hypertrophy. The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown. The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from neonatal rat hearts and cultured in vitro. Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [3H]-leucine incorporation was then measured to evaluate protein synthesis. The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression. The cell size of cardiomyocytes was also studied. Ang II (1 µM) increased cardiomyocyte hypertrophy. Similar to Ang II, treatment with 1 µM HGF promoted cardiomyocyte hypertrophy. Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes. The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.

Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration

“…The TGF-β type I receptor knockout induced an increase in Akt signalling and reduction in E3 ligase expression are likely mediated at least in part via elevated Hgf expression levels in myofibres. In both myoblasts and myotubes, HGF stimulates the Akt/mTOR pathway ( Chen et al, 2012 ; Perdomo et al, 2008 ). In addition, reduced Smad2/3 phosphorylation within myofibres likely contributes to the increase in Akt signalling and reduction in E3 ligase expression ( Goodman et al, 2013 ; Sartori et al, 2009 ).…”

Lack ofTgfbr1andAcvr1bsynergistically stimulates myofibre hypertrophy and accelerates muscle regeneration

“…The TGF-β type I receptor knockout induced an increase in Akt signalling and reduction in E3 ligase expression are likely mediated at least in part via elevated Hgf expression levels in myofibres. In both myoblasts and myotubes, HGF stimulates the Akt/mTOR pathway (A. L. Chen et al, 2012; Perdomo et al, 2008). In addition, reduced Smad2/3 phosphorylation within myofibres likely contributes to the increase in Akt signalling and reduction in E3 ligase expression (Goodman, McNally, Hoffmann, & Hornberger, 2013; Sartori et al, 2009).…”

Mechanotransduction of mesenchymal stem cells (MSCs) during cardiomyocytes differentiation

“…Interestingly, the p38-MAPK pathway involves an inhibitor known as SB203580, which has been shown to prevent HGF-induced reactions and which have been shown to suppress myogenic MSCs differentiation. It has been found that HGF therapy involving cardiomyocytes could be administered for cardiac repair, in addition, HGF is reported to play a key role in cardiomyocyte hypertrophy, moreover, Ang II is shown to increase the rate of cardiomyocytes hypertrophy ( Chen et al., 2012 ; Liao et al., 2012 ). A recent experiment conducted in a culture containing placenta-derived multipotent cells with laminin releases a significant amount of HGF secretion via Avb3/CD61 integrin, an integrin that is abundantly expressed in MSCs, reduces apoptosis and reactive oxygen species (ROS) generation in tumor necrosis factor-induced cardiomyocyte ( Moghadam et al., 2016 ).…”

“…In recent years, angiotensin AT 1 receptor through Ang II has been implicated in the development of stretch-induced heart hypertrophy in several investigations, additionally, ET-1 may play a role since ET-1 in rat heart is released when endothelial cells are stretched, and it has been demonstrated to rise in the pressure ( Chen et al., 2012 ). As a result, Ang II is released, which in turn releases ET-1.…”