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.

Figure 1.. Effects of Ang II (1 µM), HGF (10 ng/mL), and HGF (10 ng/mL) plus Ang II (1 µM) on [³H]-Leu incorporation (A), the mRNA levels of ANF (B) and the mRNA levels of β-MHC (C) in primary cardiomyocytes. N = 8 per group. The experiments were repeated three times. HGF = hepatology growth factor; Ang II = angiotensin II; ANF = atrial natriuretic factor; β-MHC = β-myosin heavy chain. ^*P < 0.05 vs control; ^#P < 0.05 vs HGF; ^&P < 0.05 vs Ang II (one-way ANOVA).

Figure 2.. Effects of Ang II (1 µM), HGF (10 ng/mL), and HGF (10 ng/mL) plus Ang II (1 µM) on average cell size. N = 8 per group. The experiments were repeated three times. HGF = hepatology growth factor; Ang II = angiotensin II. ^*P < 0.05 vs control; ^#P < 0.05 vs HGF; ^&P < 0.05 vs Ang II (one-way ANOVA).