Influence of hyperhomocysteinemia on expressions of GRP78 and CHOP in hypertensive vascular smooth muscle cells and vascular remodeling

AIM:To observe the influence of hyperhomocysteinemia (Hhcy) on the expressions of GRP78 and CHOP in hypertensive rat vascular smooth muscle cells (VSMCs) and the vascular media thickness changes and to explore the impact of homocysteine (Hcy) on vascular remodeling. METHODS: Fifty male Sprague Dawley rat models were induced by abdominal aorta constriction surgery. After 2 weeks, 24 rats with systolic blood pressure >150 mmHg were randomly and equally divided into control group (hypertensive rats fed with normal diet) and Hhcy group (hypertensive rats fed with homomethionine diet). After 4 and 8 weeks, plasma homocysteine concentration was measured by homocysteine detector. Mean arterial pressure (MAP) was measured through carotid artery incubation and aorta media thickness was measured by image analysis software. Changes of vascular morphology in rat aorta were examined by HE staining and the expressions of GRP78 and CHOP in the vascular smooth muscle cells were examined by immunohistochemistry and Western blot. RESULTS: Compared with that in control group, plasma Hcy was significantly increased in Hhcy group (P<0.01). MAP was significantly increased in both control group and Hhcy group, with no statistical significance between groups after 4 weeks (P>0.05) but with statistical significance after 8 weeks (P<0.05). Aortic media thickness in Hhcy group was significantly greater than in the control group (P<0.05). Compared with those in the control group, the cell volume and arterial thickness were significantly increased in Hhcy group. GRP78 and CHOP protein expressions in both groups increased, with that in the Hhcy group being more obvious. CONCLUSIONS: High Hcy can aggravate vascular injury and result in vascular remodeling by increasing the endoplasmic reticulum stress response of hypertensive arterial smooth muscle cells and exacerbating the unbalance between GRP78 expression and activation of CHOP.