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Suppressive effect and mechanism of saxatilin, a disintegrin from Korean snake (Gloydius saxatilis), in vascular smooth muscle cells |
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| Authors: | Young-Doug Sohn Kil-Sang Cho Sae-Ah Sun Kyu-Won Kwak Doo-Sik Kim |
| Institution: | a Cardiovascular Research Institute and Department of Medical Sciences, Yonsei University College of Medicine, Seoul 120-729, Republic of Korea b Thrombosis and Vascular Biochemistry Laboratory, Department of Biochemistry, College of Medicine, Pochon CHA University, 222 Yatap-dong, Bundang-gu, Sungnam, Kyunggi-do 463-836, Republic of Korea c National Research Laboratory for Cardiovascular Therapy, R&D Center, BioBud Inc., Seoul 153-777, Republic of Korea d Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, Republic of Korea |
| Abstract: | RGD-peptides can inhibit the binding of ligands to certain β3 integrins, αIIbβ3 and αvβ3, both of which are involved in neointimal hyperplasia that contributes to atherosclerosis and restenosis of arterial walls. Saxatilin, a disintegrin from a Korean snake (Gloydius saxatilis), interacts with integrins αIIbβ3 and αvβ3. It suppressed the adhesion of human coronary artery smooth muscle cells (HCASMCs) to vitronectin with an IC50 of 2.5 μM, and growth factor (PDGF-BB or bFGF)-induced proliferation was inhibited at an IC50 of 25 μM. Saxatilin disassembled the actin cytoskeleton of focal adhesion and induced cell detachment. This disassembly of focal adhesion in saxatilin-treated HCASMCs involved caspase-induced paxillin degradation. Saxatilin temporally phosphorylated FAK and ERKs and affected the cell cycle of HCASMCs by increasing CDK inhibitors (p21 and p27) and reducing cyclins (D1/2 and E). These results may have significant implications for integrin antagonistic therapy used for the treatment of atherosclerosis and restenosis. |
| Keywords: | Integrin Disintegrin αvβ3 Saxatilin Smooth muscle cells Proliferation Focal adhesion De-adhesion Cell cycle |
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