Abstract
Objective
Angiogenesis and inflammation are important features in atherosclerotic plaque destabilization.
The transcription factor hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulator
of angiogenesis and is also involved in inflammatory reactions. We studied HIF-1α
expression in different atherosclerotic plaque phenotypes.
Methods and results
HIF-1α expression was observed in 18/37 (49%) carotid and in 9/15 (60%) femoral endarterectomy
specimens. Expression of HIF-1α was associated with the presence of a large extracellular
lipid core (P = 0.03) and macrophages (P = 0.02). HIF-1α co-localized with vascular endothelial growth factor (VEGF), an important
downstream target of HIF-1α. In addition, a strong association was observed between
expression levels of HIF-1α and VEGF (P = 0.001). The average number of plaque microvessels was higher in plaques with no or
minor HIF-1α staining than in plaques with moderate or heavy HIF-1α staining (P = 0.03). In human macrophages, lipopolysaccharide activation induced HIF-1α expression.
In embryonic fibroblasts derived from wild-type mice, lipopolysaccharide activation
induced an increase in HIF-1α mRNA, whereas in Toll-like receptor 4 defective embryonic
fibroblasts no effect was observed after lipopolysaccharide stimulation.
Conclusions
In atherosclerotic plaque, the transcription factor HIF-1α is associated with an atheromatous
inflammatory plaque phenotype and with VEGF expression. HIF-1α expression is upregulated
in activated macrophages under normoxic conditions.
Keywords
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Article info
Publication history
Published online: July 09, 2007
Accepted:
May 22,
2007
Received in revised form:
May 12,
2007
Received:
March 24,
2007
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
