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Unbiased Glycomics in Cardio‐pulmonary Disease
Author(s) -
Ishihara Mayumi,
Zhang Hanrui,
Kumagai Tadahiro,
Stalnaker Stephanie,
Bridger Robert,
Wells Lance,
Tiemeyer Michael,
Reilly Muredach,
Azadi Parastoo
Publication year - 2015
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.29.1_supplement.lb213
Subject(s) - lactosylceramide , platelet , glycomics , platelet activation , medicine , coronary artery disease , disease , glycan , glycoprotein , immunology , biology , biochemistry , glycolipid
Cardiovascular diseases (CVD) are the most common causes of death in developed countries and their prevalence rate is rapidly growing. Understanding of changes in proteins, sphingolipids and their post‐translational modifications (PTMs) associated with disease progression are essential for elucidating the mechanisms by which these changes influence risk for CVD. Toward this end, MS analyses were performed in (a) platelets (resting, activated and sheddome preparations) of healthy humans, (b) in cultured human coronary artery endothelial cells and iPS‐derived endothelial cells and (c) in a pilot case‐control study of early onset MI cases vs. chronic coronary atherosclerosis cases vs. older disease free controls drawn from our large PennCath cohort angiographically defined patients with heart disease. For platelet study, collected resting platelets were activated in vitro. The activated‐platelet supernatant was analyzed as sheddome. Our MS analysis indicated that N‐glycans from resting and activated platelets are a mixture of high‐mannose type and complex type structures. Comparatively, those from sheddome were primarily sialylated complex type structures. The main O‐glycans in resting platelets and sheddome were O‐glucose type structures. For glycosphingolipids, expression levels of lactosylceramide and ganglioside GM3, were decreased and increased, respectively, following platelet activation. Moreover, a main glycoprotein and its PTMs in sheddome were identified by lectin blotting and proteomic/glycoproteomic analyses. Overall, our findings provided the basis for the further studies understanding the mechanism of the occurrence of CVD.