IMR Press / FBE / Volume 3 / Issue 3 / DOI: 10.2741/E301

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Hypoxia-induced ROS signaling is required for LOX up-regulation in endothelial cells
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1 Centro de Investigacion Cardiovascular (CSIC-ICCC), Hospital de la Santa Creu i Sant Pau, c/ Antoni Mª Claret 167, 08025 Barcelona, Spain
2 Departamento de Fisiologia, Facultad de Medicina, Universidad Complutense, Avda. de la Complutense s/n, 28040 Madrid, Spain

*Author to whom correspondence should be addressed.

Academic Editor: Ana Fortuno

Front. Biosci. (Elite Ed) 2011, 3(3), 955–967; https://doi.org/10.2741/E301
Published: 1 June 2011
Abstract

The adaptive response of endothelial cells to hypoxia involves a substantial remodeling of extracellular matrix (ECM). In endothelial cells hypoxia up-regulates lysyl oxidase (LOX), a key enzyme in ECM assembly, relevant to vascular homeostasis. However, the mechanism underlying this response has not been established. Hypoxia up-regulated LOX expression in endothelial cells (HUVEC and BAEC) and concomitantly increased LOX enzymatic activity. This effect was independent of autocrine factors released by hypoxic cells and relies on a transcriptional mechanism. Both mTOR blockade and HIF-1alpha knockdown slightly prevented LOX up-regulation by hypoxia, suggesting that HIF-1alpha is only partially responsible for this effect. In fact, serial promoter deletion and mutagenesis studies indicated a limited contribution of the previously described hypoxia response element (-75 bp). Interestingly, Smad over-expression further increased LOX transcriptional activity in endothelial cells exposed to hypoxia. Moreover, the increase in LOX expression triggered by hypoxia was significantly reduced by reactive oxygen species (ROS) inhibitors. Thus, our data support a role of Smad signaling and ROS in the up-regulation of LOX by hypoxia in endothelial cells.

Keywords
Endothelial Cells
Hypoxia
Reactive Oxygen Species
Lysyl Oxidase
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