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Hyperglycemia‐induced alterations of the vascular endothelium in type 2 diabetes mellitus
Author(s) -
Hoffmann Brian,
Prisco Anthony,
Widlansky Michael,
Greene Andrew
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.802.4
Subject(s) - endothelial dysfunction , endothelium , medicine , endocrinology , type 2 diabetes mellitus , endothelial stem cell , diabetes mellitus , angiotensin ii receptor type 1 , angiotensin ii , biology , receptor , in vitro , biochemistry
Endothelial dysfunction leading to coronary artery and peripheral vascular disease remains an important clinical problem in type 2 diabetes mellitus (T2DM) patients. It is known that early intensive glycemic control reduces the risk of vascular complications during T2DM, however, there is a large gap in studies of the etiology of hyperglycemia‐induced endothelial dysfunction. The objective of this study was to identify hyperglycemia‐induced alterations of endothelial signaling pathways that contribute to vascular dysfunction. Functional assays demonstrated that treatment with high glucose impairs ex vivo endothelial‐dependent vascular vasodilation and in vitro endothelial cell tube formation relative to the normal glucose control in rodent and human models. In order to identify mechanisms behind the impaired endothelial function we used glycoproteomic, phosphoproteomic and genomic methods on high glucose treated rat microvascular endothelial cells (RMVECs). Cell surface glycoproteome analysis revealed differential glycosylation of vascular targets, including the angiotensin II (AT1) and serotonin (5HT‐2A) receptors. Further analysis of gene expression and the synergistic balance of intracellular O‐GlcNAcylation/phosphorylation of treated RMVECs indicated alterations of AT1 related pathways, inflammatory factors (IL6, IL1R1a), and VEGF signaling molecules important for endothelial function. Overall, this study identified multiple hyperglycemia‐induced endothelial signaling alterations that potentially contribute to peripheral vascular disease in T2DM.