INTRODUCCIÓN: REVISIÓN CRITICA DEL PROBLEMA

CAPÍTULO IX
kinase kinase 1/2 (MEK 1/2) showed to participate in the increased proliferation
rate and in the up-regulated expression of MCP-1 and IL-8 induced by glycated
albumin in vascular smooth muscle cells 12-14 . In HUVEC, glycated albumin induced
E-selectin expression, partially depended on phosphatidylinositol 3-kinases (PI3K)
and totally depended on IkB kinase β 11 . It was also demonstrated an increased
activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)
depending on extracellular signal-regulated kinase (ERK 1/2) in macrophage RAW
cells treated with glycated albumin 15 . In fact, the activation of NF-κB and activator
protein-1 (AP-1) by glycated albumin have been described in different types of
cells 15-17 .
Furthermore, the molecular mechanism of the NOX4 and P22PHOX upregulation
induced by Amadori-glycated albumin are still undefined. In smooth muscle cells,
Nox subunits activity and transcription seemed to be regulated by Akt, MEK 1/2,
NF-κB and AP-1 18-21 whereas NF-κB regulated several NADPH oxidase subunits
expression in monocytic murine cells 22 .
To summarize, we have shown previously that gHSA up-regulates NOX4 and
P22PHOX expression leading to an enhanced ROS production in human
endothelial cells. Since increased ROS production contributes to endothelial
dysfunction, knowing the molecular mechanisms of these effects would help to find
new therapeutic solutions for some diabetic cardiovascular problems. Therefore,
our objective was to identify the regulation pathways implicated in the gHSA-
induced ROS production in human endothelial cells using pharmacological and
molecular approaches.
Material and methods
a) Cell culture
HUVEC were isolated from freshly obtained human umbilical cords donated under
informed consent of the mothers and following the method previously described [5]
with some modifications. All the procedures were approved by the Ethics
Committee for Clinical Research at Galicia (Spain), according with the World
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