Impairment of Endothelial Cell Function Induced by Hemoglobin A1c and the Potential Mechanisms

被引：4
作者：
Bo, J. [1 ]
Guan, Y. [1 ]
Guo, Y. [1 ]
Xie, S. [1 ]
Zhang, C. [1 ]
Zhang, H. [1 ]
Chen, Z. [2 ]
Lu, J. [1 ]
Meng, Q. H. [3 ]
机构：
[1] Wenzhou Med Univ, Key Lab Lab Med, Zhejiang Prov Key Lab Med Genet, Sch Lab Med & Life Sci,Minist Educ China, Wenzhou, Peoples R China
[2] Wenzhou Med Coll, Affiliated Hosp 1, Dept Lab Med, Wenzhou, Peoples R China
[3] Univ Texas MD Anderson Canc Ctr, Dept Lab Med, Houston, TX 77030 USA
来源：
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES | 2015年 / 123卷 / 09期
基金：
中国国家自然科学基金;
关键词：
diabetes mellitus; hemoglobin A(1c); HUVECs; nitric oxide; reaction oxygen species; signal pathway; ACTIVATED PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; VASCULAR SUPEROXIDE-PRODUCTION; GLYCOSYLATED HUMAN HEMOGLOBIN; TYPE-2; DIABETES-MELLITUS; SMOOTH-MUSCLE-CELLS; NAD(P)H OXIDASE; DYSFUNCTION; DISEASE; TETRAHYDROBIOPTERIN;
D O I：
10.1055/s-0035-1554622
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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.
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收藏
页码：529 / 535
页数：7
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