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Increased Levels of Advanced Glycation Endproducts in the Lenses and Blood Vessels of Cigarette Smokers

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Abstract

Background

Advanced glycation endproducts (AGEs) arise from the spontaneous reaction of reducing sugars with the amino groups of macromolecules. AGEs accumulate in tissue as a consequence of diabetes and aging and have been causally implicated in the pathogenesis of several of the end-organ complications of diabetes and aging, including cataract, atherosclerosis, and renal insufficiency. It has been recently proposed that components in mainstream cigarette smoke can react with plasma and extracellular matrix proteins to form covalent adducts with many of the properties of AGEs. We wished to ascertain whether AGEs or immunochemically related molecules are present at higher levels in the tissues of smokers.

Materials and Methods

Lens and coronary artery specimens from nondiabetic smokers and nondiabetic nonsmokers were examined by immunohistochemistry, immunoelectron microscopy, and ELISA employing several distinct anti-AGE antibodies. In addition, lenticular extracts were tested for AGE-associated fluorescence by fluorescence spectroscopy.

Results

Immunoreactive AGEs were present at significantly higher levels in the lenses and lenticular extracts of nondiabetic smokers (p < 0.003). Anti-AGE immunogold staining was diffusely distributed throughout lens fiber cells. AGE-associated fluorescence was significantly increased in the lenticular extracts of nondiabetic smokers (p = 0.005). AGE-immunoreactivity was significantly elevated in coronary arteries from nondiabetic smokers compared with nondiabetic nonsmokers (p = 0.015).

Conclusions

AGEs or immunochemically related molecules are present at higher levels in the tissues of smokers than in nonsmokers, irrespective of diabetes. In view of previous reports implicating AGEs in a causal association with numerous pathologies, these findings have significant ramifications for understanding the etiopathology of diseases associated with smoking, the single greatest preventable cause of morbidity and mortality in the United States.

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Acknowledgments

We thank T. Mitsuhashi (The Picower Institute for Medical Research) for advice on the AGE ELISA and for critical comments on the manuscript. We are extremely grateful to D. Risucci (North Shore University Hospital, NY) for statistical analyses. This work was supported by funds from The Picower Institute for Medical Research, the British Diabetic Association (A.W.S.) and the NIH (R.B.). I.D.N. and A.W.S. contributed equally to this work.

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Authors and Affiliations

  1. The Picower Institute for Medical Research, 350 Community Drive, Manhasset, New York, 11030, USA

    Iain D. Nicholl & Richard Bucala

  2. Department of Ophthalmology, The Queen’s University of Belfast, Belfast, UK

    Alan W. Stitt & Desmond B. Archer

  3. The Eye Department, The Royal Victoria Hospital, Belfast, UK

    Jonathan E. Moore

  4. Cardiothoracic Surgery Unit, Papworth Hospital, Papworth Everard, Cambridge, UK

    Andrew J. Ritchie

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  1. Iain D. Nicholl
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  2. Alan W. Stitt
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  6. Richard Bucala
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Correspondence to Iain D. Nicholl.

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Communicated by R. Bucala.

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Nicholl, I.D., Stitt, A.W., Moore, J.E. et al. Increased Levels of Advanced Glycation Endproducts in the Lenses and Blood Vessels of Cigarette Smokers. Mol Med 4, 594–601 (1998). https://doi.org/10.1007/BF03401759

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