Effects of myeloid-cell specific alpha1AMPK deletion on ATII-induced endothelial dysfunction, vascular inflammation and hypertension

• Applicants: Dr. Swenja Kröller-Schön, since 8/2018; Professor Dr. Philip Wenzel
• Subject Area: Cardiology, Angiology
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 313817099

Myelomonocytic cells play a prominent role in vascular inflammation and the associated production of reactive oxygen species (ROS). Their pathogenicity is not only determined by the vascular endothelium (e.g. by expression of adhesion molecules), but also by the phenotype of myelomonocytic cells themselves. It was recently shown that the AMP-dependent protein kinase (AMPK) plays a pivotal role for the transition of these cells from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype. Preliminary work from our own group showed that AMPK regulates ROS production in isolated myelomonocytic cells and that global AMPK deletion results in an enhanced pro-inflammatory response. Therefore, mice with a deletion of the myeloid-cell specific alpha1AMPK were generated (LysMCre+alpha1AMPKflox/flox mice), which showed increased vascular oxidative stress and impaired endothelial function during angiotensin II infusion as compared to corresponding wild-type animals. Therefore, the aim of the proposed research project is to investigate the underlying mechanisms for this vascular phenotype with an emphasis on vascular ROS production, NO signaling, inflammation and blood pressure.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Privatdozent Dr. Eberhard Schulz, until 8/2018