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Gamma Glutamyltransferase (GGT) as a Biomarkers of Atherosclerosis

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Biomarkers in Cardiovascular Disease

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Abstract

Gamma-glutamyltransferase (GGT) is an ubiquitous enzyme in human tissues that recycles precursors to the antioxidant and metabolic substrate, glutathione (GSH). GSH is critical in the dynamic preservation of antioxidant balance and in the elimination of xenobiotic substrates. When the total GSH pool becomes limited, either due to increased exposure to oxidative challenges or demand for detoxification, GGT activity increases. Related to atherosclerosis, GSH demand increases with exposure to dietary and environment exposures that have been implicated in vascular inflammation and subsequent atherosclerosis including dietary iron, lipid peroxides, advanced glycation end (AGE) products, and reduced antioxidant intake. Additional stressors on GSH balance include environmental contaminants such as persistent organic pollutants and heavy metals, which also contribute to vascular inflammation directly and indirectly due to metabolic disruption. The results of examinations of several cross-section and longitudinal cohort studies, including our results in the Multi-Ethnic Study of Atherosclerosis (MESA), demonstrate strong associations with: individual risk factors, composite cardiometabolic conditions, mechanistic atherosclerotic biomarkers, and cardiovascular events. Evaluated in totality, the existing evidence strongly suggests GGT activity is a biomarker of systemic oxidative demand indicative of active vascular inflammation, metabolic compromise, and atherosclerosis.

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Abbreviations

4-HNE:

4-Hydroxynonal

AGE:

Advanced glycation end products

CARDIA:

Coronary Artery Risk Development in Young Adults CARDIA

CRP:

C-Reactive protein

FBG:

Fasting blood glucose

FI:

Fasting insulin

FMD:

Flow-mediated dilation

GGT:

Total serum γ-glutamyltransferase activity

GSH:

Glutathione

HbA1c:

Hemoglobin A1c

HOMA-IR:

Homeostasis assessment index

IL-6:

Interleukin 6

MESA:

Multi-Ethnic Study of Atherosclerosis

NAC:

n-Acetylcysteine

oxLDL:

Oxidized LDL

sICAM-1:

Soluble intercellular adhesion molecule

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Authors and Affiliations

  1. University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92037, USA

    Ryan Bradley

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Correspondence to Ryan Bradley .

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Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

Definitions

Advanced glycation end (AGE) products

Chemical modification of food that forms from the nonenzymatic reaction between carbohydrates and proteins during cooking at high temperatures in the presence of oxygen.

C-reactive protein (CRP)

An acute phase reactant associated with immune stimulation and increased risk of cardiovascular events.

Glutathione

An antioxidant peptide consisting of glycine, cysteine, and glutamate that serves as a substrate for the enzyme glutathione peroxidase (GPx) in the reduction of lipid peroxides, and the enzyme glutathione-s-transferase (GST), which conjugates glutathione to xenobiotic compounds for elimination.

HOMA-IR

Homeostasis assessment index of insulin resistance, a mathematical model to estimate in vivo insulin resistance based on fasting glucose and fasting insulin or c-peptide.

Interleukin-6 (IL-6)

Immune cytokine that triggers acute phase inflammation and the release of acute phase reactants in the liver.

Lipid peroxides

Chemical modification of fatty acids, especially unsaturated fatty acids, when cooked at high temperatures. Lipid peroxides are substrates of glutathione-s-transferase, and thus require glutathione for elimination.

N-acetylcysteine (NAC)

An antioxidant that provides cysteine for the production of glutathione.

Oxidized LDL (oxLDL)

Oxidized low density lipoproteins are chemically oxidized lipoprotein particles that bind receptors and contribute to the formation of atherosclerotic plaques.

Soluble intracellular adhesion molecules (sICAM-1)

Endothelial receptors that bind white blood cells during the process of atherosclerosis.

γ–Glutamyltransferase (GGT)

An enzyme, previously considered a liver enzyme, that helps recycle precursors to the antioxidant peptide, glutathione.

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Bradley, R. (2015). Gamma Glutamyltransferase (GGT) as a Biomarkers of Atherosclerosis. In: Patel, V., Preedy, V. (eds) Biomarkers in Cardiovascular Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7741-5_50-1

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