Signature Protein Profiles to Identify Disease Progression and Therapeutic Modification in Murine and Human Models of Aortic Abdominal Aneurysms

• Antragsteller: Professor Dr. Lars Mägdefessel
• Fachliche Zuordnung: Kardiologie, Angiologie
• Förderung: Förderung von 2009 bis 2010
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 115077029

An abdominal aortic aneurysm (AAA) is defined as a pathologic dilatation of the infrarenal aorta that is often accompanied by significant superimposed atherosclerosis, inflammation and thrombosis. While AAAs are common and often lethal, the underlying mechanisms of formation are not well understood. Equally important, there are not adequate means to rapidly stratify risk of aneurysm development, progression, or ultimately, rupture. My hypothesis is that AAAs produce unique signature profiles of proteins that include aspects of inflammation, apoptosis, extracellular matrix breakdown and thrombosis. Thus, by interrogation of serum with custom protein microarrays, I anticipate that we will identify unique patterns of vascular-derived proteins that will serve as sensitive and specific markers of AAA development. AAAs produce and secrete specific proteins during the natural course of disease that can be interrogated in serum. The expression pattern of a mix of these proteins will be more sensitive and specific for AAA than any single protein. In addition, protein profiles can be monitored for prediction of aneurysm expansion as well as response to new therapeutical approaches like matrix-metalloproteinase-inhibitors, activators of collagen synthesis, and anti-inflammatory effects of statins. We propose to build an antibody microarray based on the previous work done at Stanford University profiling inflammatory proteins associated with atherosclerosis and supplementing this list with proteins identified by transcriptional profiling of tissue derived from human AAAs as well as predictive murine models.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeber: Professor Dr. Thomas Quertermous; Professor Dr. Philip S. Tsao, Ph.D.