Mass Spectrometry-Based Proteomic Characterization of Aortic Aneurysm Medial Degeneration in Marfan Syndrome and Congenitally Bicuspid Aortic Valve
Brandon T Larsen, Silvia Bosio, Jason D Theis, Julie A Vrana, Ahmet Dogan, Dylan V Miller. University of Arizona, Tucson, AZ; University Hospital - Parma, Parma, Italy; Mayo Clinic, Rochester, MN; Intermountain Medical Center/University of Utah, Salt Lake City, UT
Background: Medial degeneration (MD) is common in ascending aortic aneurysms in Marfan syndrome (MS) and congenitally bicuspid aortic valve (BAV). MD is thought to result from a complex sequence of events, though the cellular processes and protein level alterations are not well understood. Whether there might be detectable changes preceding overt MD that either signify a precursor state or intrinsically weaken the aortic wall is also largely unexplored.
Design: Surgical aortic tissue samples were obtained from 11 patients with MS showing MD, 7 with BAV and MD, and 9 controls without MD. Areas of MD and adjacent areas of preserved aortic media were each collected from 10 um paraffin sections by laser-capture microdissection under fluorescence microscopy (elastic fiber autofluorescence). These were digested with trypsin and analyzed by liquid chromatography electrospray tandem mass spectrometry. Raw spectral data were queried by the use of Mascot, Sequest, and X!Tandem. Peptide and protein probability scores were assigned and for each sample a list of proteins based on peptides identified by MS was generated. These lists were compared between patient groups.
Results: Substantial differences in several proteins of interest (filamin A, transgelin, β-actin, myosin 10 HC, myosin 11 HC, myosin regulatory LC 2, α3-collagen type VI, α1-collagen type III, α2-collagen type IV, fibronectin 1, EGF-containing fibulin-like extracellular matrix protein 1, clusterin, heat shock protein 3, plakoglobin, and desmoglein 3 and to a lesser extent myosin LC 6, transgelin 2, annexin A2, fibulin 1, and fibulin 5) existed in MD areas and to a lesser extent the adjacent intact media from MS and BAV samples relative to normal histology samples. MS samples had increased α1-actin in MD areas relative to MD in BAV. BAV samples showed more abundant desmoplakin in the intact media relative to MS, but these were reduced in areas of MD.
Conclusions: The aortic media in MS and BAV demonstrate unique protein expression profiles compared to normal histology controls. Some of these differences are accentuated in MD relative to areas of preserved architecture, suggesting a role in MD development and possible progression. Some these proteins may prove useful in further development of biomarkers for aneurysmal disease and progression.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 48, Monday Morning