Sulforaphane inhibits PDGF-induced proliferation of rat aortic vascular smooth muscle cell by up-regulation of p53 leading to G1/S cell cycle arrest
| Autor: | Jin-Tae Hong, Yeo-Pyo Yun, Su-Hyang Yoo, Yong Lim, Kyu-Dong Yoo, Hwan-Soo Yoo, Mi-Yea Lee, Seung-Jung Kim |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Cell cycle checkpoint Cyclin E Physiology medicine.medical_treatment Myocytes Smooth Muscle Becaplermin Muscle Smooth Vascular S Phase Rats Sprague-Dawley chemistry.chemical_compound Restenosis Isothiocyanates Internal medicine Neointima Proliferating Cell Nuclear Antigen medicine Animals Aorta Cells Cultured Cell Proliferation Pharmacology Neointimal hyperplasia biology Growth factor Cyclin-Dependent Kinase 2 G1 Phase Anatomy Cell Cycle Checkpoints Proto-Oncogene Proteins c-sis medicine.disease Rats Up-Regulation Endocrinology Carotid Arteries chemistry p21-Activated Kinases Sulfoxides biology.protein Molecular Medicine Tumor Suppressor Protein p53 Platelet-derived growth factor receptor Sulforaphane |
| Zdroj: | Vascular pharmacology. 59(1-2) |
| ISSN: | 1879-3649 |
| Popis: | Vascular diseases such as atherosclerosis and restenosis artery angioplasty are associated with vascular smooth muscle cell (VSMC) proliferation and intimal thickening arterial walls. In the present study, we investigated the inhibitory effects of sulforaphane, an isothiocyanate produced in cruciferous vegetables, on VSMC proliferation and neointimal formation in a rat carotid artery injury model. Sulforaphane at the concentrations of 0.5, 1.0, and 2.0 μM significantly inhibited platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation in a concentration-dependent manner, determined by cell count. The IC50 value of sulforaphane-inhibited VSMC proliferation was 0.8 μM. Sulforaphane increased the cyclin-dependent kinase inhibitor p21 and p53 levels, while it decreased CDK2 and cyclin E expression. The effects of sulforaphane on vascular thickening were determined 14 days after the injury to the rat carotid artery. The angiographic mean luminary diameters of the group treated with 2 and 4 μM sulforaphane were 0.25±0.1 and 0.09±0.1 mm², respectively, while the value of the control groups was 0.40±0.1 mm², indicating that sulforaphane may inhibit neointimal formation. The expression of PCNA, maker for cell cycle arrest, was decreased, while that of p53 and p21 was increased, which showed the same pattern as one in in-vitro study. These results suggest that sulforaphane-inhibited VSMC proliferation may occur through the G1/S cell cycle arrest by up-regulation of p53 signaling pathway, and then lead to the decreased neointimal hyperplasia thickening. Thus, sulforaphane may be a promising candidate for the therapy of atherosclerosis and post-angiography restenosis. |
| Databáze: | OpenAIRE |
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