Publication: Differential expressions and roles of hypoxia-inducible factor-1a, -2a and -3a in the rat carotid body during chronic and intermittent hypoxia
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Date
2008
Authors
Lam, Siu-Yin ; Tipoe, George L. ; Liong, Emily C. ; Fung, Man-Lung
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The HIF-1a expression in the carotid body
(CB) is central to the transcriptional regulation of the CB
structural and functional changes in chronic hypoxia
(CH). The CB plays pathogenic roles in cardiovascular
morbidity in patients with sleep-disordered breathing;
yet, the expression and role of HIF-a subtypes in
intermittent hypoxia (IH), resembling recurrent episodic
apnea, are unclear. We hypothesized a divergent role of
HIF-a subtypes, regulated by differential expression in
the CB response to IH. A time-course analysis of the CB
volume, and expression profiles of the HIF-1a, -2a, -3a
and HIF-regulated gene products, including vascular
endothelial growth factor (VEGF), endothelin-1 (ET-1),
and tyrosine hydroxylase (TH), showed a significant
difference in the lack of increase in the rat CB volume,
HIF-1a and VEGF expression during IH, despite an
increase in the mRNA level of HIF-1a and the
prominent increase of volume and expression in the CH
group. In contrast, there were increased CB expressions
of HIF-2a and -3a, and also ET-1 and TH in both IH
and CH groups. Results demonstrated a significant role
played by HIF-2a and -3a in the CB response to IH,
which could be complementary to the expression and
role of HIF-1a under hypoxic conditions. This differential regulation of the HIF-a subtypes and
pathways could account for the morphological and
neurochemical discrepancy in the CB responses to IH
and CH.
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