Biology Reference
In-Depth Information
Chapter 7
Hypoxia-Inducible Factors and Adenosine
Signaling in Vascular Growth
Aftab Ahmad, Carl W. White, and Shama Ahmad
Abstract Low oxygen environment or hypoxia is conducive towards vascular
growth and endothelial proliferation. Therefore it is an essential element in both
disease and development. Hypoxia stabilizes the hypoxia-inducible transcription
factors -1
and also increases adenosine levels thereby activating the
adenosine receptor signaling pathways. While these pathways have been described
independently to a greater extent, increasing evidence suggests that there is sig-
nificant crosstalk. Here we will summarize the contributions and interdependence
of hypoxia-inducible transcription factors and the adenosine receptor pathways in
vascular growth.
α
and -2
α
Keywords Angiogenesis
·
adenosine
·
A 2A receptor
·
A 2B receptor
·
Adenosine
deaminase
·
ATP
·
CD73
·
CD39
·
Hypoxia-inducible transcription fac-
tors
·
HIF-1
α ·
HIF-2
α ·
Prolyl 4-hydroxylases
·
Endothelial cells
·
Vascular
growth
·
VEGF
·
VEGFR-1
·
VEGFR-2
·
DMOG (dimethyloxalylglycine)
·
DFO
(desferrioxamine)
·
VHL (von Hippel-Lindau tumor suppressor gene product)
7.1 Introduction
Low oxygen environment or hypoxia plays a central role in complex processes such
as fetal development and diseases like cancer, sepsis and ischemic heart disease.
Physiological and pathological responses to acute and chronic hypoxia are mediated
primarily through the hypoxia-inducible transcription factors HIF-1
.
Such conditions also often cause an increase in both intracellular and extracellu-
lar levels of adenosine, and its receptors. Accumulation of extracellular adenosine
following hypoxia and/or ischemia causes activation of signaling cascades that are
geared towards maintaining homeostasis and limiting cellular damage [29]. In recent
α
and HIF-2
α
B
A. Ahmad (
)
Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA
e-mail: ahmada@njhealth.org
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