In the arterial circulation, regions of disturbed flow (DF), which
are characterized by flow separation and transient vortices, are
susceptible to atherogenesis, whereas regions of undisturbed laminar
flow (UF) appear protected. Coordinated regulation of gene expression
by endothelial cells (EC) may result in differing regional phenotypes
that either favor or inhibit atherogenesis. Linearly amplified
RNA from freshly isolated EC of DF (inner aortic arch) and UF
(descending thoracic aorta) regions of normal adult pigs was used
to profile differential gene expression reflecting the steady
state in vivo. By using human cDNA arrays, approximately 2,000
putatively differentially expressed genes were identified through
false-discovery-rate statistical methods. A sampling of these
genes was validated by quantitative real-time PCR and/or immunostaining
en face. Biological pathway analysis revealed that in DF there
was up-regulation of several broad-acting inflammatory cytokines
and receptors, in addition to elements of the NF-kappaB system,
which is consistent with a proinflammatory phenotype. However,
the NF-kappaB complex was predominantly cytoplasmic (inactive)
in both regions, and no significant differences were observed
in the expression of key adhesion molecules for inflammatory cells
associated with early atherogenesis. Furthermore, there was no
histological evidence of inflammation. Protective profiles were
observed in DF regions, notably an enhanced antioxidative gene
expression. This study provides a public database of regional
EC gene expression in a normal animal, implicates hemodynamics
as a contributory mechanism to athero-susceptibility, and reveals
the coexistence of pro- and antiatherosclerotic transcript profiles
in susceptible regions. The introduction of additional risk factors
may shift this balance to favor lesion development.