INCREASED LEVELS OF ADVANCED GLYCATION ENDPRODUCTS IN THE LENSES AND BLOOD-VESSELS OF CIGARETTE SMELTERS

Background: Advanced glycation endproducts (AGEs) arise from the spont aneous reaction of reducing sugars with the amino groups of macromolec ules. AGEs accumulate in tissue as a consequence of diabetes aad aging and have been causally implicated in the pathogenesis of several of t he end-organ complications of diabetes and aging, including cataract, atherosclerosis, and renal insufficiency. It has been recently propose d that components in mainstream cigarette smoke can react with plasma and extracellular matrix proteins to form covalent adducts with many o f the properties of AGEs. We wished to ascertain whether AGEs or immun ochemically related molecules are present at higher levels in the tiss ues of smokers. Materials and Methods: Lens and coronary artery specim ens from nondiabetic smokers and nondiabetic nonsmokers were examined by immunohistochemistry, immunoelectron microscopy, and ELISA employin g several distinct anti-AGE antibodies. In addition, lenticular extrac ts were tested for AGE-associated fluorescence by fluorescence spectro scopy. Results: Immunoreactive AGEs were present at significantly high er levers in the lenses and lenticular extracts of nondiabetic smokers (p < 0.003). Anti-AGE immunogold staining was diffusely distributed t hroughout lens fiber cells. AGE-associated fluorescence was significan tly increased in the lenticular extracts of nondiabetic smokers (p = 0 .005). AGE-immunoreactivity was significantly elevated in coronary art eries 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 precious reports implicating AG Es in a causal association with numerous pathologies, these findings h ave significant ramifications for understanding the etiopathology of d iseases associated with smoking, the single greatest prevent able caus e of morbidity and mortality in the United States.