Hypoxia-inducible factor prolyl 4-hydroxylase inhibition in cardiometabolic diseases.
Pharmacol Res
; 114: 265-273, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27832958
ABSTRACT
Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs, also called PHDs and EglNs) are enzymes that act as cellular oxygen sensors. They are the main downregulators of the hypoxia-inducible factor (HIF). HIF-P4Hs can be targeted with small molecule inhibitors, which stabilize HIF under normoxia and initiate the hypoxia response. Such inhibitors are in phase 2 and 3 clinical trials for the treatment of anemia due to their ability to induce erythropoietin and iron metabolism genes. Recent data suggest that HIF-P4H inhibition has a therapeutic role beyond anemia in cardiac ischemia, obesity and metabolic dysfunction, and atherosclerosis. The molecular level mechanisms involved are HIF stabilization driven changes in gene expression that improve perfusion and endothelial function, reprogram metabolism to promote glucose intake and glycolysis over oxidative metabolism, reduce inflammation and beneficially modify innate immune system. This review discusses the recent findings in detail.
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Base de dados:
MEDLINE
Assunto principal:
Doenças Cardiovasculares
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Prolil Hidroxilases
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Inibidores de Prolil-Hidrolase
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Doenças Metabólicas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article