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

  • Savita Bansal
  • Pawan Kumar Kare
  • Ashok Kumar Tripathi
  • Sri Venkata Madhu


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.


Cardiovascular complications Type 2 diabetes mellitus Hyperglycemia Advanced glycation end products Reactive oxygen species Oxidative stress Endothelial cells Receptor of advanced glycation end products 



8-hydroxy-2-deoxy Guanosine


Advanced glycation end products


Advanced oxidation protein products


Cardiovascular diseases


Endothelial nitric oxide synthase




Hydrogen peroxide


Glycated haemoglobin


High density lipoproteins


Hypochlorous acid


Inducible nitric oxide synthase


Low density lipoprotein


Mitogen-activated protein kinase


Monocyte-chemotactic protein-1








Methyl glyoxal lysine dimer


Nicotinamide adenine dinucleotide phosphate oxidase


nuclear factor-kappa B


Nitric oxide


Nitric oxide synthase




Oxidative stress


Poly ADP ribose polymerase


Protein carbonyls


Protein kinase C




Receptor for advanced glycation end products


Reactive oxygen species


Reactive species


Type 2 diabetes mellitus


Vascular cell adhesion molecules



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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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Savita Bansal
    • 1
  • Pawan Kumar Kare
    • 2
  • Ashok Kumar Tripathi
    • 3
  • Sri Venkata Madhu
    • 4
  1. 1.Department of Biochemistry, Institute of Home EconomicsUniversity of DelhiDelhiIndia
  2. 2.Department of BiochemistryAll India Institute of Medical Sciences (AIIMS)BhopalIndia
  3. 3.Department of BiochemistryUniversity College of Medical Sciences, University of DelhiDelhiIndia
  4. 4.Department of Medicine, Centre for Diabetes, Endocrinology & MetabolismUniversity College of Medical Sciences & Guru Teg Bahadur HospitalDelhiIndia

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