Beta4 integrin is involved in statin-induced endothelial cell death

Biochemical and Biophysical Research Communications
Chong FengMengfeng Li

Abstract

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.

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Citations

Jun 12, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Weiguo ChenJeffrey R Jacobson
Jan 27, 2010·Pharmacotherapy·Hazem F ElewaSusan C Fagan
May 4, 2018·Future Oncology·Martyna ZaleskaJacek Bil
Jun 1, 2010·Journal of Cellular Biochemistry·Weiguo ChenJeffrey R Jacobson
Apr 3, 2010·Pharmacological Reports : PR·Claudia MedaBernd Mayer
Jan 12, 2016·Journal of Cardiovascular Pharmacology·ShuYan LiuJunYing Miao
Mar 7, 2006·Seminars in Ophthalmology·Chong FengMengfeng Li
Apr 6, 2011·Journal of Cellular Physiology·Li WangJunying Miao
Jan 11, 2020·Frontiers in Oncology·Wei MuMargot Zöller
Aug 22, 2006·Vascular Pharmacology·Masaaki Ii, Douglas W Losordo

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