title: Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid.
abstract: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H2O2), have emerged as important molecules in the pathogenesis of diabetic endothelial dysfunction. Additionally, neutrophils-derived myeloperoxidase (MPO) and MPO-catalyzed hypochlorous acid (HOCl) play important roles in the vascular injury. However, it is unknown whether MPO can use vascular-derived ROS to induce diabetic endothelial dysfunction. In the present study, we demonstrated that NADPH oxidase was the main source of ROS formation in high glucose-cultured human umbilical vein endothelial cells (HUVECs), and played a critical role in high glucose-induced endothelial dysfunction such as cell apoptosis, loss of cell viability and reduction of nitric oxide (NO). However, the addition of MPO could amplify the high glucose-induced endothelial dysfunction which was inhibited by the presence of apocynin (NADPH oxidase inhibitor), catalase (H2O2scavenger), or methionine (HOCl scavenger), demonstrating the contribution of NADPH oxidase-H2O2-MPO-HOCl pathway in the MPO/high glucose-induced vascular injury. In high glucose-incubated rat aortas, MPO also exacerbated the NADPH oxidase-induced impairment of endothelium-dependent relaxation. Consistent with these in vitro data, in diabetic rat aortas, both MPO expresion and NADPH oxidase activity were increased while the endothelial function was simultaneously impaired. The results suggested that vascular-bound MPO could amplify high glucose-induced vascular injury in diabetes. MPO-NADPH oxidase-HOCl may represent an important pathogenic pathway in diabetic vascular diseases.
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Peng
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry, Jiangxi Province and College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, China. Electronic address: naihaolu@jxnu.edu.cn.
authors.forename: Naihao
authors.initials: N
authors.lastname: Lu
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000201:enzymology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014655:Vascular Resistance
chemical_list: D017382:Reactive Oxygen Species; D006997:Hypochlorous Acid; D009195:Peroxidase; D019255:NADPH Oxidases; D005947:Glucose
keywords: Diabetic vascular injury; Endothelial dysfunction; Hypochlorous acid; Myeloperoxidase; NADPH oxidase