Project Details
Projekt
Magnetic microbubble mediated vascular gene transfer for prevention of endothelial dysregulation during insulin resistance
Applicant
Privatdozentin Dr. Hanna Mannell
Subject Area
Pharmacology
Term
from 2009 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 40403621
Gene targeting of the vasculature offers numerous therapeutic possibilities as conditions associated with vascular dysfunction, such as insulin resistance or type 2 diabetes mellitus, foster vascular disease and thus represent a great socioeconomic problem. By associating therapeutic lentiviral particles or plasmid DNA to magnetic microbubbles and their trapping and rupture at a specific site using external magnetic fields and ultra sound the side effects of systemic gene therapy are reduced and gene transfer efficiencies enhanced. The tyrosine phosphatase SHP-2 regulates PI3-K/Akt and MAPK pathway activation, which is disturbed in insulin resistance, upon growth factor stimulation and influences angiogenesis. The aim of this study is to investigate whether SHP-2 is involved in endothelial insulin signalling and if modulation of SHP-2 can be used to restrict the endothelial dysfunction and its consequences on angiogenesis and vascular inflammation in insulin resistance. This shall be achieved by using the technique of site-directed magnetic microbubble assisted gene delivery of mutant forms of SHP-2 in the vasculature in vivo.
DFG Programme
Research Units
Participating Person
Professor Dr. Florian Krötz
