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Mechanistic Investigation of Reversal of Endothelial Dysfunction in hyperglycemia
Author(s) -
Patel Hemang,
Chen Juan,
Kavdia Mahendra
Publication year - 2016
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.30.1_supplement.948.10
Subject(s) - endothelial dysfunction , superoxide dismutase , catalase , reactive oxygen species , nitric oxide , endocrinology , medicine , oxidative stress , chemistry , apocynin , superoxide , endothelium , hydrogen peroxide , diabetes mellitus , vasodilation , pharmacology , nadph oxidase , biochemistry , enzyme
Progression of endothelial dysfunction has emerged as a significant risk factor for diabetes related complications such as retinopathy, nephropathy, neuropathy and vascular dementia. At elemental level, endothelial dysfunction results from and into disproportionate changes in vasoactive reactive oxygen species (ROS). Superoxide (O 2 − ), nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ) regulates the redox state of dysfunctional endothelium. Increased O 2 − levels rapidly react away with NO to reduce its bioavailability, which sets the stage for endothelial dysfunction in hyperglycemia. Simultaneous regulation in H 2 O 2 levels supports either vasoconstrictive or vasorelaxative processes. Several therapeutic strategies had limited success to manage endothelial dysfunction and results from these strategies have shown a lack of understanding of the redox interplay. We studied the regulation of overall redox state and endothelial function during hyperglycemia. We measured O 2 − , NO, and H 2 O 2 levels using dihydroethidium (DHE), DAF‐FM diacetate and Amplex Red assay, respectively, during sodium nitrite (NaNO 2 ), superoxide dismutase (SOD) and catalase treatments in hyperglycemia treated HUVECs. Hyperglycemia significantly increased O 2 − and H 2 O 2 levels and decreased NO levels in HUVECs. Treatments to exogenous SOD and NaNO 2 decreased O 2 − levels and significantly increased NO levels in hyperglycemic‐HUVECs. Similarly, treatment with catalase also induced similar changes in O 2 − and NO levels. Our results suggest that besides the O 2 − and NO, regulation of H 2 O 2 levels also serves a viable therapeutic alternative for improving the redox state of hyperglycemic‐HUVECs. These results also suggest that production of NO, O 2 − and H 2 O 2 is tightly regulated in hyperglycemia‐induced endothelial dysfunction. The indirect manipulation of the fate of O 2 − may hold a key to reverse and manage the hyperglycemic‐endothelial dysfunction. Support or Funding Information This study was funded by NIHR01 HL084337