Things get broken: the hypoxia-inducible factor prolyl hydroxylases in ischemic heart disease

  • Timm Schreiber
  • Luca Salhöfer
  • Theresa Quinting
  • Joachim FandreyEmail author
Invited Review


A major challenge in developing new treatments for myocardial infarction (MI) is an improved understanding of the pathophysiology of hypoxic tissue damage and the activation of endogenous adaptive programs to hypoxia. Due to the relevance of oxygen in metabolism, molecular adaptation to hypoxia driven by the hypoxia-inducible factors (HIFs) and the HIF-regulating prolyl hydroxylase domain enzymes (PHDs) is pivotal for the survival of cells and tissue under hypoxia. The heart under ischemic stress will extensively rely on these mechanisms of endogenous cardiac protection until hypoxia becomes too severe. In the past, work from several laboratories has provided evidence that inhibition of HIF-regulating PHDs might improve the outcome in ischemic heart disease (IHD) potentially because the adaptive mechanisms are boosted early and vigorously. Here, we review the role of the HIF hydroxylase pathway in IHD and highlight the potential of PHD inhibitors as a new treatment for MI with special regard to acute ischemia, reperfusion, and regeneration of the heart.


Ischemia Reperfusion Regeneration HIF PHD Heart 


Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of PhysiologyUniversity of Duisburg-EssenEssenGermany

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