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

In this study, we first found that HGF could induce cardiomyocyte hypertrophy. To our surprise, the HGF-induced cardiomyocyte hypertrophy was even greater than Ang II-induced hypertrophy ( Figure 1A-C) . The presence of the HGF receptor on cardiomyocytes was first confirmed by Akiyama et al. (28) . Subsequently, several independent reports have demonstrated a protective effect of HGF on myocardial infarction in vivo (29, 30) . However, as yet the underlying mechanisms for the pro-hypertrophy of cardiomyocytes are not clear. Moreover, the results of in vivo experiments cannot exclude the possibility that HGF treatment stimulates cardiac fibroblasts (31) and thereby releases factors that induce hypertrophy of the surrounding cardiomyocytes. Pathological cardiomyocyte hypertrophy is characterized not only by an increase in cardiomyocyte size, but also by cardiomyocyte gene reprogramming, as shown by the enhanced expression of fetal phenotypes of genes, such as skeletal α-actin, β-MHC, and ANF (32) . In our study, we evaluated cell hypertrophy by determining [ 3 H]-Leu incorporation and the average cell size as well as ANF and β-MHC mRNA levels. Based on these various parameters, we have clearly shown that HGF can directly induce cardiomyocyte hypertrophy. It should be noted that Nakamura et al. (33) demonstrated an interference of administered HGF on cardiomyopathy remodeling in hamster hearts. The authors found a direct negative effect of HGF on the transcript levels of ANF. In the present study, we showed an inductive effect of HGF on ANF levels, in agreement with a previous report (34) . We considered that this disparity might be due to the species difference.