β4 integrin is involved in statin-induced endothelial cell death

被引:19
作者
Feng, C
Ye, CS
Liu, XN
Ma, H
Li, MF [1 ]
机构
[1] Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Cardiol, Guangzhou 510080, Peoples R China
关键词
HMG-CoA reductase; statins; endothelial cells; angiogenesis; beta; 4; integrin;
D O I
10.1016/j.bbrc.2004.08.171
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
HMG-CoA reductase inhibitors (statins) have been shown to inhibit angiogenesis. The molecular mechanism mediating the anti-endothelial activities of statins remains unclear. The present study demonstrated that the antiangiogenic effect of atorvastatin (ATV) was associated with endothelial death. Molecular profiling data identified a 29-fold upregulation of beta4 integrin mRNA. Western blot and flow cytometry confirmed robust increases of total and cell-surface beta4 integrin. Blockage of beta4 integrin activity by antagonizing antibody abrogated ATV-induced endothelial death. The endothelial death and beta4 Integrin upregulation by ATV could be reversed by intermediate metabilites of the HMG-CoA reductase pathway mevalonate or GGPP, but not by FPP, suggesting that these effects were results of specific inhibition of the pathway. These data indicate that the HMG-CoA reductase might represent an important survival pathway in angiogenic endothelial cells and thus, a potential target for antiangiogenic therapy. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:858 / 864
页数:7
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