Preclinical Development of Gene Therapy: The Effects of Urocortin 2 and Urocortin 3 Gene Transfer in Murine Models of Heart Failure and Diabetes

Dimosthenis Giamouridis

Research output: ThesisDoctoral ThesisExternal prepared

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Abstract

Cardiovascular disease is leading cause of death in the western societies, with dismal outlook even upon optimal treatment which underlines the necessity of better therapies. Urocortin-2 and urocortin-3 intravenous infusion improved heart function in humans. However, constant administration of these proteins is required for chronic treatment due to their short half-life (few minutes), a problem that could be solved by gene transfer of those peptides. This work demonstrates that one intravenous injection of adeno-associated virus encoding urocortin-2 or urocortin-3 increases cardiac function in mice. Furthermore, urocortin-2 gene transfer increased insulin sensitivity in mice. These findings support urocortin-2 and urocortin-3 gene transfer as potential treatment for heart failure and diabetes.
Original languageEnglish
Awarding Institution
  • Maastricht University
Supervisors/Advisors
  • Biessen, Erik, Supervisor
  • Hammond, H. Kirk, Supervisor, External person
  • Blankesteijn, Matthijs, Advisor
Award date5 Jun 2019
Place of PublicationMaastricht
Publisher
Print ISBNs9789463236683
DOIs
Publication statusPublished - 2019

Keywords

  • Gene therapy
  • Heart failure
  • Insulin sensitivity
  • contractile function
  • diastolic function
  • adeno-associated virus

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