title: Impairment of Endothelial Cell Function Induced by Hemoglobin A(1c) and the Potential Mechanisms.
abstract: OBJECTIVE
  Hemoglobin A(1c) (HbA(1c)) concentrations reflect glycemic control and diabetic complications. However, there is little evidence supporting the pathological role of HbA(1c) in the development and progression of diabetic complications. We investigated the impact of HbA(1c) on endothelial cell function and the potential mechanisms.
  
  
  METHODS
  The effects of HbA(1c) on the viability and migration of human umbilical vein endothelial cells (HUVECs) were measured by the Cell Counting Kit-8 and a wound healing scratch assay, respectively. Production of nitric oxide (NO) and reactive oxygen species was measured by the nitrate reductase colorimetric method and flow cytometry, respectively. The expression of endothelial nitric oxide synthase (eNOS) mRNA was quantitated by reverse-transcriptase PCR. The expression of eNOS, p-AMPK, and NOX4 proteins was detected by Western blot.
  
  
  RESULTS
  High concentrations of HbA(1c) reduced the viability and migration of HUVECs in a dose- and time-dependent manner. High concentrations of HbA(1c) inhibited production of NO but increased production of ROS. Incubation with increasing concentrations of HbA(1c) downregulated the expression of eNOS mRNA, decreased expression of eNOS and p-AMPK, and upregulated expression of NOX4.
  
  
  CONCLUSIONS
  These findings provide direct evidence that HbA(1c) is involved in the development and progression of the cardiovascular complications of diabetes.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Bo
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Xie
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Q H
authors.initials: QH
authors.lastname: Meng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D055372:AMP-Activated Protein Kinases; D006442:Glycated Hemoglobin; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D017382:Reactive Oxygen Species; C517652:hemoglobin A1c protein, human; C496314:NOS3 protein, human; C498910:NOX4 protein, human