Context-Dependent Regulation of Nrf2/ARE Axis on Vascular Cell Function during Hyperglycemic Condition

Tharmarajan Ramprasath; Allen John Freddy; Ganesan Velmurugan; Dhanendra Tomar; Balakrishnan Rekha; Vemparthan Suvekbala; Subbiah Ramasamy

doi:10.2174/1573399816666200130094512

Context-Dependent Regulation of Nrf2/ARE Axis on Vascular Cell Function during Hyperglycemic Condition

Curr Diabetes Rev. 2020;16(8):797-806. doi: 10.2174/1573399816666200130094512.

Authors

Tharmarajan Ramprasath¹, Allen John Freddy², Ganesan Velmurugan³, Dhanendra Tomar⁴, Balakrishnan Rekha¹, Vemparthan Suvekbala⁵, Subbiah Ramasamy¹

Affiliations

¹ Department of Molecular Biology, School of Biological Sciences, Madurai Kamaraj University, Madurai 625021, Tamil Nadu, India.
² Department of Zoology, Madras Christian College, Chennai 600 059, Tamil Nadu, India.
³ Chemomicrobiomics Laboratory, KMCH Research Foundation, Kovai Medical Center & Hospital, Coimbatore 641 014, Tamil Nadu, India.
⁴ Center for Translational Medicine, Temple University, Philadelphia 19140, United States.
⁵ Department of Biomedical Sciences & Technology, Noorul Islam Centre for Higher Education, Kumaracoil, Thucklay, Tamilnadu 629180, India.

PMID: 32000646
DOI: 10.2174/1573399816666200130094512

Abstract

Diabetes mellitus is associated with an increased risk of micro and macrovascular complications. During hyperglycemic conditions, endothelial cells and vascular smooth muscle cells are exquisitely sensitive to high glucose. This high glucose-induced sustained reactive oxygen species production leads to redox imbalance, which is associated with endothelial dysfunction and vascular wall remodeling. Nrf2, a redox-regulated transcription factor plays a key role in the antioxidant response element (ARE)-mediated expression of antioxidant genes. Although accumulating data indicate the molecular mechanisms underpinning the Nrf2 regulated redox balance, understanding the influence of the Nrf2/ARE axis during hyperglycemic condition on vascular cells is paramount. This review focuses on the context-dependent role of Nrf2/ARE signaling on vascular endothelial and smooth muscle cell function during hyperglycemic conditions. This review also highlights improving the Nrf2 system in vascular tissues, which could be a potential therapeutic strategy for vascular dysfunction.

Keywords: Nrf2/ARE; endothelial cells; oxidative stress; phase II antioxidant enzymes; smooth muscle cells; vascular dysfunction.

Publication types

Review

MeSH terms

Animals
Antioxidant Response Elements / genetics*
Antioxidant Response Elements / physiology
Antioxidants / metabolism
Diabetes Complications / genetics
Diabetes Complications / metabolism
Diabetes Complications / physiopathology
Diabetes Mellitus, Type 2 / complications
Diabetes Mellitus, Type 2 / genetics*
Diabetes Mellitus, Type 2 / metabolism
Diabetes Mellitus, Type 2 / physiopathology
Diabetic Angiopathies / genetics
Diabetic Angiopathies / metabolism
Diabetic Angiopathies / physiopathology
Endothelial Cells / metabolism*
Epigenesis, Genetic
Gene Expression Regulation / genetics
Gene Expression Regulation / physiology
Humans
Hyperglycemia / genetics*
Hyperglycemia / metabolism
Kelch-Like ECH-Associated Protein 1 / genetics
Kelch-Like ECH-Associated Protein 1 / metabolism
Myocytes, Smooth Muscle / metabolism*
NF-E2-Related Factor 2 / genetics*
NF-E2-Related Factor 2 / metabolism
Oxidation-Reduction
Oxidative Stress / genetics
Oxidative Stress / physiology
Phosphotransferases / genetics
Phosphotransferases / metabolism
Reactive Oxygen Species / adverse effects
Reactive Oxygen Species / metabolism
Signal Transduction / genetics
Signal Transduction / physiology

Substances

Antioxidants
Kelch-Like ECH-Associated Protein 1
NF-E2-Related Factor 2
NFE2L2 protein, human
Reactive Oxygen Species
Phosphotransferases