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Erschienen in: Cardiovascular Drugs and Therapy 6/2022

17.09.2021 | Invited Review Article

Prolyl Hydroxylase Inhibitors: a New Opportunity in Renal and Myocardial Protection

verfasst von: Juan Antonio Requena-Ibáñez, Carlos G. Santos-Gallego, Anderly Rodriguez-Cordero, M. Urooj Zafar, Juan José Badimon

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 6/2022

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Abstract

Hypoxia, via the activity of hypoxia-inducible factors (HIFs), plays a crucial role in fibrosis, inflammation, and oxidative injury, processes which are associated with progression of cardiovascular and kidney diseases. HIFs are key transcription heterodimers consisting of regulatory α-subunits (HIF-1α, HIF-2α, HIF-3α) and a constitutive β-subunit (HIF-β). The stability of HIFs is regulated by the prolyl hydroxylases (PHDs). Specific PHD inhibitors (PHD-i) are being investigated as a therapeutic approach to modulate the cellular signaling pathways and harness the native protective adaptive responses to hypoxia. Selective inhibition of PHD leads to the stabilization of the HIFs, which is the transcriptional gatekeeper of a multitude of genes involved in angiogenesis, energy metabolism, apoptosis, inflammation, and fibrosis. PHD-i downregulate hepcidin, improve iron absorption, and increase the endogenous production of erythropoietin. Furthermore, this pharmacological group has also been proven to ameliorate ischemic injuries in several organs, opening a new and promising field in cardiovascular research.. In this review, we present the basic and clinical potential of PHD-i treatment in different scenarios, such as ischemic heart disease, cardiac hypertrophy and heart failure, and their interplay with other pharmacological agents with proven cardiovascular benefits, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors.
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Metadaten
Titel
Prolyl Hydroxylase Inhibitors: a New Opportunity in Renal and Myocardial Protection
verfasst von
Juan Antonio Requena-Ibáñez
Carlos G. Santos-Gallego
Anderly Rodriguez-Cordero
M. Urooj Zafar
Juan José Badimon
Publikationsdatum
17.09.2021
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 6/2022
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-021-07257-0

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