Prevention of the secondary cerebral organ damage by stimulation of the AT2-receptor and the receptor Mas in a model of acute lung injury

• Applicant: Professor Dr. Mario Menk
• Subject Area: Anaesthesiology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 423491678

This project evaluates the therapeutic potential of a direct stimulation of the AT2 receptor and the receptor Mas on the secondary cerebral organ damage in a model of acute lung injury. Main goal of this project is to demonstrate that pharmacological activation of these two receptors using the specific agonists Compound 21 (C21) and AVE0991 might be a successful, therapeutic strategy in treatment of the acute lung injury on the one hand, and also in prevention of the secondary cerebral organ damage on the other hand. Focus of the project is the characterization of the pulmonary and cerebral inflammation, the quantification of the organ damage and the evaluation of cellular mechanisms involved in cell death and survival such as apoptosis and autophagy. Also, the project aims to describe, at least in part, the underlying signaling pathways via a down-regulation of the ERK-cascade. A distant goal and also the vision of this project is to describe a new, potentially beneficial treatment strategy for patients with acute respiratory distress syndrome. To date, there are no specific pharmacological interventions available to improve outcomes or to attenuate secondary organ damages in these patients. From the clinical perspective, a new intervention strategy for these critically-ill patients would be worthwhile. In this respect, the project comprises fundamental research to this topic. Positive experimental results given, clinical studies could be conducted to evaluate the principle of a AT2/receptor Mas activation in patients with acute lung failure.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Roland Francis; Clarissa von Haefen, Ph.D.