Regulation and function of AMPK in endothelial cells

• Applicant: Professorin Dr. Regine Heller
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 115424795

The AMP-activated protein kinase (AMPK) plays a role in endothelial cell energy supply, stress protection and maintaining an antiinflammatory and antiatherogenic phenotype. The present project on AMPK regulation and function in endothelial cells will focus on two goals. We will prove the hypothesis that AMPK contains an inhibitory phosphorylation site and that targeting this site may be an approach to affect AMPK activity. We will further investigate whether and how AMPK is involved in the regulation of endothelial barrier function and how it controls endothelial cell migration. We hypothesize that AMPK activated at low energy state will preserve endothelial structure and junctions. In contrast, AMPK activated via receptor-dependent signalling pathways may support barrier disruption and cell movement. To verify this hypothesis, we will investigate the role of different pathways of AMPK stimulation, characterize AMPK targets related to the regulation of endothelial structure and perform functional assays in vitro and in mice with genetically ablated AMPK a1 subunit (permeability, migration, angiogenesis). We expect that the data obtained in this project will contribute to the development of pharmacological strategies targeting endothelial dysfunction.

• DFG Programme: Research Grants