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Oxidative Stress in Heart Diseases pp 437–459Cite as

Advanced Glycation End Products: A Potential Contributor of Oxidative Stress for Cardio-Vascular Problems in Diabetes

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Abstract

Growing incidence of cardio-vascular complications is a global health concern in type 2 diabetes mellitus (T2DM) and it is now progressively understood in mechanistic terms. The multiple pathways that are associated with cardiovascular diseases (CVD) in T2DM seem to share a common element involving persistent hypergylcemia and oxidative stress (OS). Advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions in diabetes is increasingly evidence as one of the major pathway for excess generation of free radicals and OS, which exacerbates the development and progression of cardiovascular complications. AGE-induced OS is a major risk factor for myocardial cell death, hypertrophy, inflammation, vasoconstriction, pro-thrombotic gene expression, fibrosis and endothelial cell dysfunction.

AGEs mediate their pathological effects either directly through modification of soluble, cellular and extracellular matrix proteins by affecting their structure, functions and enzymatic activities. Such moderations of proteins result in disrupting the matrix-matrix and matrix-cell interaction contributing to pro-fibrotic effect. AGEs can also mediate their effect by activating signaling cascades via the receptor for advanced glycation end products (RAGE). AGE-RAGE interaction initiates a complex series of intracellular signaling resulting in enhanced production of ROS leading to OS development, cytokines production (TGF-β1 and CTGF), nuclear factor-kappa B (NF-κB) activation, cellular proliferation, and others that may possibly exacerbate the damaging effects on cardiac function in diabetes. Therefore, AGEs may be one of the important factor acts as a crucial mediator of hyperglycemic-mediated detrimental effects in diabetes and represent a novel therapeutic target for the treatment of cardiovascular complications. Also, anti-AGEs strategies acting synergistically with conventional approaches may play an important role in the amelioration of vascular complications associated with diabetes.

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Abbreviations

8-OHdG:

8-hydroxy-2-deoxy Guanosine

AGEs:

Advanced glycation end products

AOPP:

Advanced oxidation protein products

CVD:

Cardiovascular diseases

eNOS:

Endothelial nitric oxide synthase

GO:

Glyoxal

H2O2 :

Hydrogen peroxide

HbA1C :

Glycated haemoglobin

HDL:

High density lipoproteins

HOCl:

Hypochlorous acid

iNOS:

Inducible nitric oxide synthase

LDL:

Low density lipoprotein

MAPK:

Mitogen-activated protein kinase

MCP 1:

Monocyte-chemotactic protein-1

MDA:

Malondialdehyde

MGO:

Methylglyoxal

MGO:

Methylglyoxal

MOLD:

Methyl glyoxal lysine dimer

NADPH:

Nicotinamide adenine dinucleotide phosphate oxidase

NF-κB:

nuclear factor-kappa B

NO:

Nitric oxide

NOS:

Nitric oxide synthase

ONOO− :

Peroxynitrite

OS:

Oxidative stress

PARP:

Poly ADP ribose polymerase

PCO:

Protein carbonyls

PKC:

Protein kinase C

PON1:

Paraoxonase

RAGE:

Receptor for advanced glycation end products

ROS:

Reactive oxygen species

RS:

Reactive species

T2DM:

Type 2 diabetes mellitus

VCAM 1:

Vascular cell adhesion molecules

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Acknowledgments

This work was supported by the Indian Council of Medical Research, Government of India, New Delhi and the Council of Scientific and Industrial Research, New Delhi, India.

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India

    Savita Bansal

  2. Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, India

    Pawan Kumar Kare

  3. Department of Biochemistry, University College of Medical Sciences, University of Delhi, Delhi, India

    Ashok Kumar Tripathi

  4. Department of Medicine, Centre for Diabetes, Endocrinology & Metabolism, University College of Medical Sciences & Guru Teg Bahadur Hospital, Delhi, India

    Sri Venkata Madhu

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  1. Savita Bansal
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  2. Pawan Kumar Kare
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  3. Ashok Kumar Tripathi
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  4. Sri Venkata Madhu
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Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Sciences, St Boniface Hospital, Albrechtsen Research Centre, Winnipeg, MB, Canada

    Naranjan S Dhalla

  3. Translational Health Science and Technology (THSTI), Department of Biotechnology, Faridabad, India

    Nirmal K Ganguly

  4. Translational Health Science and Technology (THSTI), Department of Biotechnology, Faridabad, India

    Madhu Dikshit

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Bansal, S., Kare, P.K., Tripathi, A.K., Madhu, S.V. (2019). Advanced Glycation End Products: A Potential Contributor of Oxidative Stress for Cardio-Vascular Problems in Diabetes. In: Chakraborti, S., Dhalla, N., Ganguly, N., Dikshit, M. (eds) Oxidative Stress in Heart Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-13-8273-4_20

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