Exploring the physiological role of a natriuretic peptide glycoform in cardiorenal function.

PhD defence by Peter Fruergaard Andersen

Assessment Committee

Associate professor Morten Scheibye-Knudsen, Department of Cellular and Molecular Medicine, University of Copenhagen (Chairperson)
Professor Bodil Steen Rasmussen, University Hospital of Aalborg
Professor Adrian Hobbs, Queen Mary University of London - The William Harvey Research Institute - Faculty of Medicine and Dentistry

Supervisors

Associate Professor Katrine Schjoldager
Clinical Professor Jens Peter Gøtze
Clinical Associate Professor David Peick Sonne

Department

Department of Cellular and Molecular Medicine

Graduate Programme

Cellular and Genetic Medicine

Place

Building: Maersk Building, floor 1, Room: Holst Auditoriet, Blegdamsvej 3B, 2200 København N.

Email address to gain access to the thesis: peteran@sund.ku.dk.
You will either receive a copy of the thesis or be informed where you can read a physical copy.
Recipients of copies of the thesis are not allowed to share or distribute it due to copyright compliance.

Short description of the thesis

The heart acts as an endocrine organ: when the atria are stretched by rising blood volume, they secrete atrial natriuretic peptide (ANP), a hormone that lowers blood pressure, promotes salt and water excretion by the kidneys, and restrains fluid-retaining systems. Its therapeutic use has been limited by a very short half-life and risk of hypotension. This thesis characterised a naturally occurring O-glycosylated form of ANP (gANP) on which the peptide is carrying a small sugar modification. Across a first-in-human infusion study and a hypertensive-rat model, glycosylation reduced clearance and prolonged circulating half-life roughly five-fold while partly preserving the blood-pressure-lowering and renal effects. Notably, ANP’s acute metabolic actions were absent with gANP. Glycosylation thus dissociates ANP’s benefits from its liabilities.