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Advanced glycation end-products and atherosclerosis
1Picower Institute for Medical Research, Manhasset, NY 11030, USA.
Annals of Medicine
|October 1, 1996
Summary
Advanced glycation end-products (AGEs) and their degradation products (AGEp) accumulate in tissues, contributing to diabetic complications. These AGEs and AGEp act as toxins, potentially accelerating glucose toxicity in susceptible individuals.
Area of Science:
- Biochemistry
- Pathology
- Nephrology
Background:
- Advanced glycation end-products (AGEs) are formed by nonenzymatic glucose modification of proteins and accumulate in diabetic and aging tissues.
- AGEs trigger cellular responses via AGE-specific receptors (AGEr), contributing to vascular dysfunction and sclerosis.
- AGE degradation products, AGE peptides (AGEp), are cleared by the kidneys, with clearance inversely related to renal function.
Purpose of the Study:
- To investigate the role of AGEs and AGEp in diabetic complications and renal disease.
- To understand the mechanism by which AGEp contribute to tissue damage and toxicity.
Main Methods:
- Analysis of AGE and AGEp levels in relation to renal function.
- Characterization of AGEp modifications, including AGEp-collagen and AGEp-LDL formation.
- Correlation of AGE-modified LDL levels with renal failure and atherosclerosis susceptibility.
Main Results:
- Circulating AGEp levels correlate inversely with renal creatinine clearance.
- AGEp can covalently bind to collagen and LDL, forming AGEp-collagen and AGEp-LDL.
- Patients with renal failure exhibit elevated levels of AGE-modified LDL, suggesting increased atherosclerosis risk.
Conclusions:
- Both glucose-derived AGEs and endogenously produced AGEp function as distinct toxins.
- AGEp can amplify tissue damage and accelerate glucose toxicity, particularly in genetically susceptible individuals.
- Elevated AGEp and AGE-modified LDL are associated with renal failure and increased atherosclerosis risk in diabetic patients.