LOX-1 and ROS, inseparable factors in the process of endothelial damage

Abstract

Lectin-like oxidized low-density lipoprotein (LOX-1) has been identified in endothelial cells as the main receptor of oxidized low-density lipoprotein (OxLDL). LOX-1 is upregulated in the presence of pathological conditions including atherosclerosis, hypertension, and diabetes because it acts as a mediator of “endothelial dysfunction”. It promotes the generation of superoxide anion (O₂⁻), the inhibition of nitric oxide (NO) production and the increment of endothelial adhesiveness to monocytes. Recently, it was reported that OxLDL, binding to LOX-1, determined a significant increase in the generation of reactive oxygen species (ROS), suggesting the involvement of signaling pathways such as mitogen-activated protein kinases (MAPKs).

It is now generally accepted that ROS act indirectly on the modulation of LOX-1 expression because ROS oxidize native LDL. Moreover, LOX-1 activation per se may stimulate ROS generation. Accordingly, our findings showed that high levels of ROS can directly increase LOX-1 production in microvascular endothelial cells (HMEC-1).

It has been reported that OxLDL, usually > 20 μg protein/ml, induced apoptosis in a variety of cell types. At low concentrations (< 5 μg protein/ml) OxLDL appears to be associated with cell proliferation and low levels of ROS-induced capillary tube formation in endothelial cells.

Our data and those of the literature indicate the existence of a direct control of LOX-1 by ROS.

Although ROS in large amounts clearly have detrimental effects on cell biology, small amounts of ROS could have a beneficial effect, suggesting its therapeutic potential for reducing ischemic tissue.

Keywords::

• Ox-LDL receptors
• free radicals
• oxidative stress
• endothelial function
• angiogenesis

Acknowledgements

The authors are grateful to Lucrecia Mota Garcia for her English editing support and to Alison Frank for the final English revision.

Declaration of interest

The authors report no declarations of intererst. The authors alone are responsible for the content and writing of the paper.