Focal Expression of Angiotensin II Type 1 Receptor and Smooth Muscle Cell Proliferation in the Neointima of Experimental Vein Grafts

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Abstract
—Eddy flow has been shown to promote focal smooth muscle cell (SMC) proliferation and neointimal formation in experimental vein grafts. This study focuses on whether the angiotensin II type 1 (AT 1 ) receptor mediates these events. Experimental vein grafts with and without eddy flow were created in the rat. Losartan was used to assess the influence of the AT 1 receptor on SMC proliferation. In vein grafts with eddy flow, apparent focal expression of AT 1 mRNA and protein was found in the leading region of the proximal focal neointima, where eddy flow occurred, but not in the trailing region, where eddy flow diminished, at days 5, 10, 20, and 30. The rate of SMC proliferation in the leading region (10.9±1.4%, 19.5±2.2%, 12.2±2.0%, and 6.9±1.3% at these times, respectively) was significantly higher than that in the trailing region (9.5±1.8%, 15.3±2.0%, 8.2±1.9%, and 3.2±0.7%) in these vein grafts. When eddy flow was prevented in engineered vein grafts, no apparent location difference was found in the distribution of AT 1 receptor mRNA and protein in the neointima, and the rate of SMC proliferation (5.3±1.0%, 5.8±0.9%, 3.4±1.0%, and 3.7±0.9% at days 5, 10, 20, and 30, respectively) was reduced significantly. In vein grafts with losartan, the rate of SMC proliferation in the leading region of the neointima (9.4±1.8%, 10.1±1.3%, 8.3±0.9%, and 4.2±0.5% at days 5, 10, 20, and 30, respectively) was significantly lower than that in vein grafts without losartan. These results suggested that eddy flow upregulated the AT 1 receptor, which in turn mediated focal SMC proliferation in the neointima of experimental vein grafts.