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Can hyperglycemia‐induced endothelial dysfunction be reversed by regulating the fate of superoxide?
Author(s) -
Patel Hemang,
Chen Juan,
Kavdia Mahendra
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.979.8
Subject(s) - endothelial dysfunction , superoxide , superoxide dismutase , nitric oxide , catalase , endothelium , hydrogen peroxide , endocrinology , reactive oxygen species , medicine , chemistry , endothelial stem cell , pharmacology , oxidative stress , biochemistry , enzyme , in vitro
Increased superoxide (O₂‾) levels and diminished nitric oxide (NO) are hallmarks of hyperglycemia‐induced endothelial dysfunction. As per the literature increased O₂‾ levels rapidly reacts away with NO to reduce its bioavailability, which sets the stage for endothelial dysfunction in hyperglycemia. With that perspective several therapeutic strategies were tried out to improve NO levels through neutralizing O₂‾ to manage endothelial dysfunction. However, the limited outcomes from these strategies have raised concerns on current understanding of the interplay that drives the fate of O₂‾ to regulate the functionality of endothelial cells. Thus, we investigated the effects of regulating fate of O₂‾ on endothelial function during hyperglycemia. Using systems biology approach, we monitored the interplay amongst superoxide (O₂‾), nitric oxide (NO), and hydrogen peroxide (H₂O₂) during superoxide dismutase (SOD) and catalase treatments in hyperglycemia treated HUVEC. Hyperglycemia significantly increased O₂‾ and H₂O₂levels and decreased NO levels in endothelial cells. However, the treatments with exogenous SOD decreased O₂‾ levels and significantly increased NO levels in hyperglycemic HUVEC. Surprisingly, treatment with catalase also inflicted the similar changes. Our results suggest that manipulating either O₂‾ or H₂O₂ levels can improve NO levels during hyperglycemia‐induced endothelial dysfunction. These results also suggest that production of O₂‾ and H₂O₂ is tightly regulated in hyperglycemia‐induced endothelial dysfunction. Thus, manipulating the fate of O₂‾ may hold a key to reverse the endothelial dysfunction.