Rahiman, Abdul Jaleel Abdul

Background Structural and functional mitral valve abnormalities are commonly encountered in the general population. In order to determine which functional protein classes may be important to normal valve function we performed the first reported comprehensive proteomic profiling of structurally normal human mitral valves. Methods We harvested mitral valve leaflets from 5 patients who underwent orthotopic cardiac transplantation for cardiomyopathy. The morphologic appearance of mitral valves was normal with only mild functional mitral regurgitation on echocardiogram. High resolution 2D gel electrophoresis was performed to separate proteins. Gel spots were excised from 2 representative samples and protein identification was carried out using liquid chromatography tandem mass spectrometry. Results We identified 190 unique proteins with >99% probability and at least 2 unique peptides. The proteins were from various cellular locations, including cell surface, cytoskeleton, endoplasmic reticulum, extracellular matrix, mitochondrion, nucleus, cytoplasm, and plasma membrane. Functional clustering revealed that the identified proteins were involved in major molecular pathways including, energy along with fatty acid metabolism, calcium signaling acute phase response & oxidative stress, and anti‐apoptosis pathways. Conclusion Proteomic profiling of the normal human mitral valve demonstrates a pattern of expression suggesting multiple biological functions. Further quantification of protein levels and comparison with diseased mitral valves will provide new insights into the etiology and therapy of mitral valve disease in humans.