Expression of GRP78 and CHOP in aortic vascular smooth muscle cells of hypertension rats and its effect on vascular remodeling

AIM: To clarify the effect of endoplasmic reticulum stress (ERS) on vascular remodeling induced by hypertension and to investigate the expression of the correlation factors: glucose-regulated protein of 78 kD (GRP78) and CAAT/enhancer binding protein homologous protein (CHOP), apoptosis of aortic vascular smooth muscle cells (VSMCs) and the aortic media thickness of hypertensive rats. METHODS: Forty-eight Sprague Dawley (SD) adult rats were divided randomly into two groups: the sham operation group (control group) and the surgical model group. Each group was subdivided into 3-, 7-, 14- and 28-day subgroups according to the different time of ending the experiment after the surgery. Each subgroup had six rats. After blood pressure of rats was measured, expression of GRP78 and CHOP in aortic VSMCs was detected by immunohistochemistry staining, apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) and aortic media thickness was measured by image analyses software. RESULTS: Mean arterial blood pressure (MAP) of the 3-, 7-, 14- and 28-day subgroups in the model group was (141.90±9.01),(150.42±6.29),(158.00±8.54),and (174.00±8.25)mmHg, respectively, and was significantly higher than MAP of the corresponding subgroups in the control group ［(115.06±8.85), (123.85±9.85), (118.48±7.60), (120.08±8.85)mmHg, respectively (P<0.05)］ in a time-dependent manner. Except for that of the 3-day subgroup, the expression of GRP78 of the 7-, 14-, and 28-day subgroups in the model group, whose absorbance (A) value was 0.60±0.04, 0.85±0.06, 0.55±0.06 in turn, was significantly higher (P<0.01), with A value peaking on day 14 compared with that of the corresponding subgroups in the control group (0.47±0.01, 0.47±0.03, 0.47±0.02, respectively). The expression of CHOP of 14- and 28-day subgroups in the model group, whose A value was 0.60±0.04, 0.85±0.06, 0.55±0.06, respectively, increased significantly (P<0.01) compared with that of their corresponding subgroups in the control group (0.40±0.02, 0.40±0.01, respectively) and the expression reached a peak on day 28 in the model group. No significant difference was observed in A value of the 3- and 7-day subgroups (0.41±0.05, 0.41±0.04, respectively) in the model group compared with that of the corresponding subgroups in the control group (0.39±0.03, 0.39±0.03, respectively). Apoptosis rate of the vascular smooth muscle cells in the 3-, 7-, 14- and 28-day subgroups of the model group was (18.20±0.03)%, (12.00±0.03)%, (6.60±0.02)% and (2.30±0.02)%, respectively, and decreased significantly compared with that of the corresponding subgroups in the control group ［(21.40±0.04)%, (20.90±0.04)%, (20.50±0.04)% and (21.30±0.04)%, respectively (P<0.01］. No significant difference was observed in media thickness of the 3- and 7-day subgroups in the model group compared with that of the corresponding subgroups in the control group. Media thickness of the 14- and 28-day subgroups in the model group was (100.32±2.92)μm, (107.52±5.42)μm, respectively, and increased significantly (P<0.01) compared with that of the corresponding subgroups in the control group ［(93.43±2.73)μm, (92.92±3.17)μm, respectively］. In the model group no significant difference was observed in the media thickness between the 3- and 7-day subgroups but significant intergroup difference was observed in the media thickness (P<0.01) between the other groups. CONCLUSION: ERS is induced in VSCMs during the early development of hypertension, which leads to the increase of mismatched expression of GRP78 and CHOP and a decrease in the rate of apoptosis. This may be one cause of vascular remodeling.