Inhibition of endothelial cell migration by cerivastatin, an HMG‐CoA reductase inhibitor: contribution to its anti‐angiogenic effect

FEBS Letters

Vincent, Loı̈c¹  Chen, Wenming¹  Mirshahi, Farrokh¹  Mirshahi-Khorassani, Tooran²  Soria, Claudine¹  Vannier, Jean-Pierre¹  Hong, Li¹  Soria, Jeannette²  Mishal, Zohair³ 

[1] Laboratoire DIFEMA, UFR de Médecine et Pharmacie de Rouen, 22 Boulevard Gambetta, 76183 Rouen, France;Laboratoire de Biochimie et EMI 99-12, Hôtel-Dieu, Paris, France;CNRS, IFR 2249, Villejuif, France

关键词: Anti-angiogenesis;    Migration;    HMG-CoA reductase inhibitor;    Cerivastatin;    RhoA;    Ras;    HMG-CoA;    3-hydroxy-3-methyl-glutaryl-coenzyme A;    MMP;    matrix metalloproteinase;    bFGF;    basic fibroblast growth factor;    VEGF;    vascular endothelial growth factor;    OSM;    oncostatin M;    MVA;    mevalonate;    FPP;    farnesylpyrophosphate;    GGPP;    geranylgeranylpyrophosphate;    HMEC;    human microvascular endothelial cell(s);    FCS;    fetal calf serum;    PBS;    phosphate-buffered saline;    RT-PCR;    reverse transcriptase-polymerase chain reaction;   

DOI  :  10.1016/S0014-5793(01)02337-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recent studies have suggested that inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (statins) can play a role in protection against vascular risk, which is independent of cholesterol reduction. It could act by inhibiting the synthesis of isoprenoids (farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP)), which are respectively essential for membrane attachment and biological activity of GTPases Ras and RhoA. This study demonstrates that a statin (cerivastatin) inhibits angiogenesis. This effect was due to a decrease in endothelial cell locomotion which was reversed by GGPP. It was mainly related to delocalization of RhoA from cell membrane to cytoplasm, responsible for the disorganization of actin stress fibers. Furthermore, a decrease in MMP-2 secretion, involved in cell invasion, was also observed. This effect is rather due to Ras inhibition as it was reversed by FPP. This anti-angiogenic activity could explain the beneficial effect of statins on atherosclerosis and on cancer prevention as shown by clinical studies.

【 授权许可】

Unknown