<Original> Atorvastatin promoted in vitro angiogenesis by reduction of geranylgeranyl pyrophosphate in a dose-dependent manner and protected against rho kinase-mediated endothelial cell damage caused by thromboxane A2
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[Abstract] Background: Atorvastatin can inactivate Rho/Rho kinase via a reduction in the synthesis of geranylgeranyl pyrophosphate (GGPP).Thromboxane A2 (TxA2) causes endothelial cell (EC) apoptosis via Rho/Rho kinase activation.We tested the hypothesis that atorvastatin protects against the Rho kinase-mediated anti-angiogenic effect of TxA2. Methods: We used human coronary artery ECs to form tubular structures on plates coated with a basement membrane matrix gel. The number of tubular structure was counted under a microscope. The caspase-3 activity was used as a determinant of apoptosis.Results: Atorvastatin significantly increased the number of tubes in a dose-dependent manner, and this effect was blocked by mevalonate or geranylgeranyl pyrophosphate (GGPP). Similar to atorvastatin, a potent selective inhibitor of geranylgeranyl transferase type I enhanced tubular formation. A TxA2 mimetic (IBOP) inhibited formation of EC tubular structures. The inhibitory effect was completely blocked by a TxA2 antagonist (SQ29548), a Rho kinase inhibitor (Y27632), and by atorvastatin. The IBOP-induced increase in caspase-3 activity was attenuated by atorvastatin. Conclusions: Atorvastatin promoted in vitro angiogenesis of ECs in a dose-dependent manner and reversed the TxA2 receptor-mediated antiangiogenic effect. We suggest that reduction of GGPP and inactivation of Rho kinase plays an important role in the proangiogenic effect of atorvastatin.
Departmental Bulletin Paper
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収録刊行物
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- ACTA MEDICA KINDAI UNIVERSITY
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ACTA MEDICA KINDAI UNIVERSITY 43 (1), 35-42, 2018-06
Kindai University Medical Association
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詳細情報 詳細情報について
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- CRID
- 1050001202540335104
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- NII論文ID
- 120006492819
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- ISSN
- 03866092
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- 本文言語コード
- en
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- 資料種別
- departmental bulletin paper
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- データソース種別
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- IRDB
- CiNii Articles