Role of Vasodilator Stimulated Phosphoprotein (VASP) during Hypoxia, Inflammation and Ischemia-Reperfusion Injury.

• Applicant: Professor Dr. Peter Rosenberger
• Subject Area: Anaesthesiology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 128859549

Limited oxygen availability (hypoxia) is the end result for a variety of pathological conditions, such as shock, sepsis and inflammation. Hypoxia and acute inflammatory processes results in conformational changes of the cytoskeleton. This process is associated with a disruption of cellular barriers, a mainstay of the human organism to defend its integrity and might result in organ dysfunction. Vasodilator phosphostimulated protein (VASP) is a crucial cytoplasmatic actin binding protein controlling paracellular permeability as well as activation of thrombocytes. VASP expression is reduced during periods of hypoxia resulting in reduced cellular endothelial and epithelial barrier function. This has significant implications on organ protection during periods of systemic inflammation and ischemia reperfusion-injury. Our preliminary data demonstrate a crucial role of VASP for the alveolar-capillary barrier during acute lung injury and during periods of hypoxia. VASP also has significant impact during myocardial, hepatic and gastrointestinal ischemiareperfusion injury and on gastrointestinal barrier properties. Therefore we propose here to investigate the role of VASP and VASP expression on the vascular integrity and organ function during periods of acute inflammation, hypoxia and ischemiareperfusion injury. Taken together, these studies are aimed to identify novel innate metabolic and transcriptional pathways to maintain organ function and integrity during conditions of hypoxia, acute inflammation and reperfusion-injury. Extensions of these findings will help to identify novel molecular targets in the treatment of critical illnesses.

• DFG Programme: Research Grants