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

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, induding cataract, atherosderosis, 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.

Simple non-invasive assessment of advanced glycation endproduct accumulation

“…The majority of the ten control subjects with higher autofluorescence values than their matched diabetic patient had smoked for many years. Tobacco smoke contains fluorescent cross-linking proteins and increases plasma AGE [32]. In diabetic patients, skin autofluorescence was not related to smoking, possibly due to the low number of smokers in the diabetic population.…”

“…Renal dysfunction in diabetic patients, but also in euglycaemic patients, contributes to increased tissue AGE accumulation and to the development of cardiovascular complications in these patients [3,12,13]. Smoking, which is recognised as a source of oxidative stress in vivo [32], was also correlated with increased skin autofluorescence in control subjects. The majority of the ten control subjects with higher autofluorescence values than their matched diabetic patient had smoked for many years.…”

“…Wolffenbuttel et al [31] observed a slower decline in haemoglobin-AGE, the AGE-modified form of haemoglobin, than in HbA 1 c in diabetic patients switching to a more intensive regimen. AGE skin levels increase in parallel with the accumulation of AGE in other organs [5] and correlate with early manifestations of nephropathy and retinopathy independently of HbA 1 c [8,32,33].…”

Lens ageing as an indicator of tissue damage associated with smoking and non-enzymatic glycation - a twin study

“…The value of twin A is plotted against the value of twin B lens yellowing and formation of advanced glycation end products. Substances in tobacco smoke can induce advanced glycation end products identical to those formed by glucose [22] and the amount of advanced glycation end products is increased in the lenses and blood of smokers irrespective of diabetes [22,23]. Smoking has previously been implicated in the pathogenesis of macrovascular complications in Type II diabetic patients [24].…”

Role of Exogenous Advanced Glycation End Products in Oral Carcinogenesis: A Review

“…Reactive glycation products derived from chewing tobacco extract and smoke are capable of interacting with proteins rapidly to form AGEs and have been detected in higher levels in smokers than controls irrespective of diabetes [18]. Such AGEs promote "metabolic memory" in the body, wherein previous exposure to tobacco glycotoxins causes damage to tissue that is not reversed by cessation of habit [19].…”