Journal
CIRCULATION RESEARCH
Volume 117, Issue 1, Pages 65-79Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.117.305109
Keywords
dioxygenases; hypoxia; hypoxia inducible factor; prolyl hydroxylases
Funding
- Wellcome Trust
- Ludwig Institute for Cancer Research
- British Heart Foundation [RG/11/1/28684] Funding Source: researchfish
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Hypoxia inducible factors (HIFs) are / heterodimeric transcription factors that direct multiple cellular and systemic responses in response to changes in oxygen availability. The oxygen sensitive signal is generated by a series of iron and 2-oxoglutarate-dependent dioxygenases that catalyze post-translational hydroxylation of specific prolyl and asparaginyl residues in HIF subunits and thereby promote their destruction and inactivation in the presence of oxygen. In hypoxia, these processes are suppressed allowing HIF to activate a massive transcriptional cascade. Elucidation of these pathways has opened several new fields of cardiovascular research. Here, we review the role of HIF hydroxylase pathways in cardiac development and in cardiovascular control. We also consider the current status, opportunities, and challenges of therapeutic modulation of HIF hydroxylases in the therapy of cardiovascular disease.
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