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Systems biology framework for studying hyperglycemia‐induced endothelial dysfunction (676.19)
Author(s) -
Patel Hemang,
Chen Juan,
Kavdia Mahendra
Publication year - 2014
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.28.1_supplement.676.19
Subject(s) - endothelial dysfunction , endothelial stem cell , oxidative stress , biology , reactive oxygen species , phenotype , microbiology and biotechnology , gene , gene expression , endothelium , endocrinology , medicine , biochemistry , in vitro
Current understandings of endothelial dysfunction mechanism have failed to provide guidelines for a system wide treatment of endothelial dysfunction. In this study, we investigated and compared the effects of high glucose on HUVEC and HMVEC using a systems biology approach. Following high glucose exposure, gene expression levels of several redox enzymes, ROS neutralizing enzymes, and oxidative stress activated transcription factor were compared in both endothelial cell types. The functional changes of superoxide (O₂‾), hydrogen peroxide (H₂O₂), and mitochondrial membrane polarization (MMP) were measured in endothelial cell. Results illustrated a consistent increase of O₂‾ levels, in both endothelial cells. However, there was a variable change in underlying gene expression profile and H₂O₂ and MMP levels, during high glucose exposure in these two endothelial cells. The results showed that a hallmark increase of O₂‾ in endothelial cells across human vasculature could be a result of variable involvement of gene expression and functional changes. Our findings highlighted a unique framework for hyperglycemia‐induced endothelial dysfunction. Identifying genomic phenotype and corresponding functional changes in hyperglycemic endothelial dysfunction will provide a suitable systems biology approach for understanding underlying mechanisms and possible effective therapeutic intervention. Grant Funding Source : NIH R01 HL084337