Angiogenic transcriptome of human microvascular endothelial cells: Effect of hypoxia, modulation by atorvastatin

A Loboda, A Jazwa, A Jozkowicz, G Molema, J Dulak*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

42 Citaten (Scopus)


Hypoxia changes expression of angiogenic genes. Statins were also reported to affect blood vessel formation. However, data on the effects of statins on endothelial cells in hypoxia are limited. Here, effect of hypoxia and atorvastatin was assessed in human microvascular endothelial cells (HMEC-1). Hypoxia (1% O-2) up-regulated vascular endothelial growth factor-A (VEGF-A) but, unexpectedly, it decreased interleukin-8 (IL-8) and placenta growth factor (PIGF) expression. Atorvastatin (0.1 - 1 mu M) attenuated PIGF in HMEC-1 in normoxia while it decreased VEGF-A and IL-8 production both in normoxia and hypoxia. Notably, the expression of VEGF-D, macrophage scavenger receptor-1 (MSR1), transforming growth factor beta receptor III (TGF beta R3) and inhibitor of DNA binding 3 (ID3) was augmented by atorvastatin in cells cultured in normoxia, while in hypoxia the statin attenuated their expression. These data showed that hypoxia influenced in the opposite way the expression of major endothelial genes, augmenting VEGF-A and decreasing IL-8 and PIGF. The influence of atorvastatin on angiogenic gene expression is complex, and final pro- or anti-angiogenic outcome of statin therapy remains to be established for numerous angiogenesis-related diseases. (c) 2005 Elsevier Inc. All rights reserved.

Originele taal-2English
Pagina's (van-tot)206-214
Aantal pagina's9
TijdschriftVascular pharmacology
Nummer van het tijdschrift4
StatusPublished - apr.-2006

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