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

Chen, Ai-Lan; Ou, Cai-Wen; He, Zhao-Chu; Liu, Qi-Cai; Dong, Qi; Chen, Min-Sheng

One limitation of this study is that the molecular mechanisms underlying the combined effect of Ang II and HGF on cardiomyocyte hypertrophy remain to be elucidated. It has been reported that post-infarction HGF gene therapy resulted in substantial cardiomyocte hypertrophy at the edges of the infarcted tissue, accompanied by the overexpression of the HGF receptor (c-Met), which is a transmembrane tyrosine kinase through which HGF activates the Ras-Raf-MEK-ERK signaling pathway, thereby contributing to myocardial hypertrophy (38) . The c-Met is also a receptor for the scatter factor (SF) (39) . The activation of c-Met by HGF/SF can elicit a variety of cellular responses including proliferation, migration, invasion, and branching morphogenesis. These processes are associated with several signaling pathways such as PI3K/Akt, Src, and STAT3 (39) . Moreover, these signaling pathways also contribute to Ang II-induced hypertrophy. Aoki et al. (40) have shown that the ERK pathway has an important role in Ang II-induced cardiac hypertrophy. Moreover, the PI3K/Akt, Src, and STAT3 pathways have also been reported to be vital controllers in Ang II-induced cardiac hypertrophy. Therefore, it may be difficult to determine the exact underlying molecular mechanisms of the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. The convergence point between HGF and Ang II needs to be further elucidated in future experiments. Our study has provided the first evidence that HGF and Ang II administered in combination induce cardiomyocyte hypertrophy. This finding was supported by the changes observed in protein synthesis, the presence of fetal phenotypes of gene expression (ANF and β-MHC), an increase in cell size, and ultrastructural changes of neonatal cardiomyocytes. These results may help to improve the management and treatment of patients with cardiac hypertrophy.