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Therapeutic inhibition of prolyl hydroxylase domain-containing enzymes in surgery: putative applications and challenges

Authors Harnoss JM, Strowitzki MJ, Radhakrishnan P, Platzer L, Harnoss JC, Hank T, Cai J, Ulrich A, Schneider M

Received 25 October 2014

Accepted for publication 13 November 2014

Published 30 January 2015 Volume 2015:3 Pages 1—14

DOI https://doi.org/10.2147/HP.S60872

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Dörthe Katschinski


Jonathan Michael Harnoss, Moritz Johannes Strowitzki, Praveen Radhakrishnan, Lisa Katharina Platzer, Julian Camill Harnoss, Thomas Hank, Jun Cai, Alexis Ulrich, Martin Schneider

Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany


Abstract: Oxygen is essential for metazoans to generate energy. Upon oxygen deprivation adaptive and protective pathways are induced, mediated by hypoxia-inducible factors (HIFs) and prolyl hydroxylase domain-containing enzymes (PHDs). Both play a pivotal role in various conditions associated with prolonged ischemia and inflammation, and are promising targets for therapeutic intervention. This review focuses on aspects of therapeutic PHD modulation in surgically relevant disease conditions such as hepatic and intestinal disorders, wound healing, innate immune responses, and tumorigenesis, and discusses the therapeutic potential and challenges of PHD inhibition in surgical patients.

Keywords: hypoxia, HIF, PHD, PHI, surgery

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