Olmesartan inhibits the expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α and improves vascular remodeling after vascular injury in mouse

摘要

Objective: To investigate the neointima formation and the expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in cuff-induced vascular injury in mouse model, and to examine the effect of angiotensin Ⅱ type 1 receptor (AT_1) blocker, olmesartan, on MCP-1 and TNF-α expression and consequently vascular remodeling. Methods: Vascular injury was induced by polyethylene cuff-placement around the mouse femoral artery. Some mice were treated with AT_1 receptor blocker, olmesartan, at the dose of 3 mg·kg~(-1)·day~(-1) with an osmotic minipump. Neointima formation and the proliferation of vascular smooth muscle cells ( VSMCs) were measured by morphometric analysis and bromodeoxyuridine ( BrdU) incorporation. MCP-1 and TNF-α expression was detected by Western blot and immunohistochemical staining. Results: We observed neointima formation 14 days after cuff placement as well as VSMCs proliferation in the media and neointima. Cuff placement also induced MCP-1 and TNF-α expression in the media and neointima that the VSMCs specifically existed. Treatment of mice with olmesartan at a dose of 3 mg·kg~(-1)·day~(-1), which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs, Olmesartan also inhibited MCP-1 and TNF-α expression in the injured arteries. Conclusions: Our results demonstrate that blockade of AT_1 receptor inhibits MCP-1 and TNF-α expression and thereby improves vascular remodeling.