Impairment of Endothelial Cell Function Induced by Hemoglobin A(1c) and the Potential Mechanisms

J Bo; Y Guan; Y Guo; S Xie; C Zhang; H Zhang; Z Chen; J Lu; Q H Meng

doi:10.1055/s-0035-1554622

Impairment of Endothelial Cell Function Induced by Hemoglobin A(1c) and the Potential Mechanisms

Exp Clin Endocrinol Diabetes. 2015 Oct;123(9):529-35. doi: 10.1055/s-0035-1554622. Epub 2015 Jun 11.

Authors

J Bo¹, Y Guan¹, Y Guo¹, S Xie¹, C Zhang¹, H Zhang¹, Z Chen², J Lu¹, Q H Meng³

Affiliations

¹ 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.
² Department of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
³ Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA.

PMID: 26069073
DOI: 10.1055/s-0035-1554622

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.

Conclusion: These findings provide direct evidence that HbA(1c) is involved in the development and progression of the cardiovascular complications of diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / biosynthesis
Cell Survival / drug effects
Female
Gene Expression Regulation / drug effects
Glycated Hemoglobin / pharmacology*
Human Umbilical Vein Endothelial Cells / metabolism*
Human Umbilical Vein Endothelial Cells / pathology
Humans
Male
NADPH Oxidase 4
NADPH Oxidases / biosynthesis
Nitric Oxide / metabolism
Nitric Oxide Synthase Type III / biosynthesis
Reactive Oxygen Species / metabolism
Wound Healing / drug effects

Substances

Glycated Hemoglobin A
Reactive Oxygen Species
hemoglobin A1c protein, human
Nitric Oxide
NOS3 protein, human
Nitric Oxide Synthase Type III
NADPH Oxidase 4
NADPH Oxidases
NOX4 protein, human
AMP-Activated Protein Kinases