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Differential but Complementary HIF1? and HIF2? Transcriptional Regulation.


ABSTRACT: Effective vascular regeneration could provide therapeutic benefit for multiple pathologies, especially in chronic peripheral artery disease (PAD) and myocardial ischemia. The hypoxia inducible factors (HIFs) mediate the cellular transcriptional response to hypoxia and regulate multiple processes that are required for angiogenesis to ultimately restore perfusion and oxygen supply. In endothelial cells, both HIF1? and HIF2? are known to contribute to this role; however, the extent and individual roles of each of these HIF? remain unclear. To characterize the individual roles of HIF?, we sequenced the transcriptional outputs of stabilized forms of HIF1? and HIF2?, where they regulated 701 and 1,454 genes, respectively. HIF1? transcription primarily regulated metabolic reprogramming, whereas HIF2? exerted a larger role in regulating angiogenic extracellular signaling, guidance cues, and extracellular matrix remodeling factors. Furthermore, HIF2? almost exclusively regulated a large and diverse subset of transcription factors and coregulators that contribute to its diverse roles in hypoxia. Further understanding of how HIFs regulate cellular processes in hypoxia and angiogenesis could offer new avenues to modulate physiological angiogenesis to enhance revascularisation in ischemic conditions and other pathologies.

SUBMITTER: Downes NL 

PROVIDER: S-EPMC6036226 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Differential but Complementary HIF1α and HIF2α Transcriptional Regulation.

Downes Nicholas L NL   Laham-Karam Nihay N   Kaikkonen Minna U MU   Ylä-Herttuala Seppo S  

Molecular therapy : the journal of the American Society of Gene Therapy 20180509 7


Effective vascular regeneration could provide therapeutic benefit for multiple pathologies, especially in chronic peripheral artery disease (PAD) and myocardial ischemia. The hypoxia inducible factors (HIFs) mediate the cellular transcriptional response to hypoxia and regulate multiple processes that are required for angiogenesis to ultimately restore perfusion and oxygen supply. In endothelial cells, both HIF1α and HIF2α are known to contribute to this role; however, the extent and individual r  ...[more]

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