Format

Send to

Choose Destination
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1890-3. doi: 10.1161/ATVBAHA.109.190678. Epub 2009 Aug 20.

Disinhibition of SOD-2 expression to compensate for a genetically determined NO deficit in endothelial cells--brief report.

Author information

1
Department of Clinical Chemistry, University Medicine Göttingen, Germany.

Abstract

OBJECTIVE:

Homozygosity for the -786C-variant of the human nos-3 gene is a risk factor for coronary artery disease (CAD). Interestingly, affected individuals develop CAD more frequently but not earlier than the general population.

METHODS AND RESULTS:

Genotyped primary human umbilical vein endothelial cells (ECs) were exposed to fluid shear stress (FSS) and analyzed for nitric oxide (NO) and superoxide anion (O(2)(-)) formation as well as mRNA and protein expression of different antioxidant enzymes. Dysfunctional CC-genotype ECs failed to upregulate NO synthase expression in response to FSS and exhibited a reduced NO synthesis capacity when compared to functionally intact TT-genotype ECs. However, only CC-genotype ECs responded to FSS with an Egr-1-mediated increase in manganese-containing superoxide dismutase (SOD-2) expression, shielding them from endothelin-1-induced oxidative stress in a NO-independent manner.

CONCLUSIONS:

This FSS-induced rise in SOD-2 expression in CC-genotype ECs effectively stabilizes their antiatherosclerotic phenotype and may explain not only the comparatively slow onset of CAD in homozygous carriers of the C-allele of the nos-3 gene but also define a general strategy for preventing endothelial dysfunction at the outset of atherosclerosis.

PMID:
19696404
DOI:
10.1161/ATVBAHA.109.190678
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center