Abstract 12772: Quantitative Protein Profiling of Human Aortic Valves Reveals Protein Patterns Related to Calcific Stenosis
Background: Calcific Aortic Valve Stenosis (CAVS) is a major valvular disease affecting a significant percentage of the elderly population. It shares many hallmarks with atherosclerosis such as lipid accumulation, inflammation and calcium deposition. However, only about half of the patients with CAVS have clinically significant atherosclerosis which implies that many of the specific mechanisms remain to be discovered. We used a 2-D differential gel electrophoresis (2-D DIGE) to study the proteomic changes involved in CAVS.
Methods and Results: Total protein was extracted from severely stenotic aortic valves of patients undergoing valve replacement surgery (n = 8) and non-sclerotic control valves from patients with aortic insufficiency (n = 5). Protein samples were labelled with fluorescent Cy3/Cy5 dyes prior to isoelectric focusing on a broad pH range (pH 3-10) followed by separation by molecular mass. Resulting protein patterns were analysed and a total of 17 statistically significant changes were discovered. These protein spots were extracted and subjected to matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for identification. Among the identified proteins were the receptor for tissue-type plasminogen activator (Annexin II) and heat shock protein 90 alpha (HSP90α). Gene onthology analysis revealed that Annexin II plays an important role in angiogenesis, collagen fibril organization and fibrinolysis. HSP90α is a molecular chaperone involved in multiple processes such as stress, apoptosis and cell cycle. Interestingly, also Annexin II seems to be a potential target for HSP90α mediated structural modification.
Conclusion: To the best of our knowledge, this is the first report of a proteomic approach to characterising the pathogenesis of CAVS. We report several novel components that have not been previously implicated in the disease. Involvement of Annexin II and HSP90α in CAVS provides intriguing new aspects in to the progression of the disease.
- © 2011 by American Heart Association, Inc.