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

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...

Full description

Saved in:
Bibliographic Details
Published in:Cardiovascular drugs and therapy 2022-12, Vol.36 (6), p.1187-1196
Main Authors: Requena-Ibáñez, Juan Antonio, Santos-Gallego, Carlos G., Rodriguez-Cordero, Anderly, Zafar, M. Urooj, Badimon, Juan José
Format: Article
Language:English
Subjects:
Angiogenesis
Apoptosis
Cardiology
Cardiovascular diseases
Congestive heart failure
Coronary artery disease
Energy metabolism
Erythropoietin
Fibrosis
Heart diseases
Hepcidin
Hydroxylase
Hypertrophy
Hypoxia
Hypoxia-inducible factor 1a
Hypoxia-inducible factors
Inflammation
Inhibitors
Invited Review Article
Ischemia
Kidney diseases
Medicine
Medicine & Public Health
Na+/glucose cotransporter
Pharmacology
Prolyl hydroxylase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0920-3206
1573-7241
DOI:10.1007/s10557-021-07257-0