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Integrating MALDI Imaging Mass Spectrometry and Shotgun Proteomics for a Systems Biology Understanding of Congenital Heart Valve Disease
Author(s) -
Angel Peggi M,
Mettler Brett M,
Bichell David P,
Baldwin H. Scott,
Caprioli Richard M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.209.5
Subject(s) - extracellular matrix , proteomics , thymosin , proteome , microbiology and biotechnology , mass spectrometry , elastin , chemistry , shotgun proteomics , fibulin , focal adhesion , computational biology , biology , biochemistry , signal transduction , genetics , chromatography , gene
Our objective is to define protein regulation and interaction involved in cellular microenvironments of congenital aortic valve stenosis (CAVS) towards therapies delaying valve deterioration. We are using matrix‐assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) to identify pathology related protein distributions within CAVS leaflets. Protein interaction networks (PINs) are constructed around MALDI IMS protein nodes from proteomic data produced using multidimensional protein identification technology (MudPIT). We illustrate the technique with a case study of bicuspid CAVS. MALDI IMS showed 39/44 novel proteins following patterns of extracellular matrix disarray. MudPIT identified 2238 proteins with main pathways of focal adhesion, leukocyte transendothelial migration, and complement system, indicating a primary component of immune response. Spatially defined PINs showed thymosin beta 4 involved in cytoskeletal organization within areas of glycosaminoglycans. Thymosin beta 10 overlapping with S100A6 expression in areas of elastin was implicated in regulation of adhesion and structural development. These studies may be applied to other areas of cardiovascular biology.