Effect of Udenafil on Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rat Carotid Artery Injury Model

Background and ObjectivesVascular smooth muscle cell (VSMC) proliferation is responsible for the restenosis of previously inserted coronary stents. Angiotensin II (Ang II) is known to regulate VSMC proliferation. LKB1, a serine/threonine kinase, interacts with the p53 pathway and acts as a tumor suppressor.Materials and MethodsWe assessed the association of Ang II and the expression of LKB1 in primary cultured murine VSMCs and neointima of the Sprague Dawley rat carotid artery injury model. We created carotid balloon injuries and harvested the injured carotid arteries 14 days after the procedure.ResultsAng II increased LKB1 expression in a time-dependent manner and peaked at an Ang II concentration of 10-7 mole/L in VSMCs. In the animal experiment, neointima was markedly increased after balloon injury compared to the control group. Immunohistochemical studies showed that LKB1 expression increased according to neointima thickness. Ang II augmented LKB1 expression after the injury. Western blot analysis of LKB1 with carotid artery lysate revealed the same pattern as LKB1 immunohistochemistry. Increased LKB1 expression started at 5 days after the balloon injury, and peaked at 14 days after the injury. Although LKB1 expression was increased after the injury, LKB1 kinase activity was not increased. Ang II or balloon-injury increased the expression of LKB1 although the LKB1 activity was reduced.ConclusionAng II increased LKB1 expression in VSMCs and neointima. These findings were not kinase dependant.

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Tumor Suppressor Serine/Threonine Kinase LKB1 Expression, Not Kinase Activity, Increased in the Vascular Smooth Muscle Cells and Neointima in the Rat Carotid Artery Injury Model

Jeong

Kim

Ahn

et al. 2010

Korean Circ J

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Effect of Udenafil on Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rat Carotid Artery Injury Model

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Tumor Suppressor Serine/Threonine Kinase LKB1 Expression, Not Kinase Activity, Increased in the Vascular Smooth Muscle Cells and Neointima in the Rat Carotid Artery Injury Model

Tumor Suppressor Serine/Threonine Kinase LKB1 Expression, Not Kinase Activity, Increased in the Vascular Smooth Muscle Cells and Neointima in the Rat Carotid Artery Injury Model

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