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01-03-2004 | Leading Article

Advanced Glycation Endproduct Crosslinking in the Cardiovascular System

Potential Therapeutic Target for Cardiovascular Disease

Authors: Dr Susan J. Zieman, David A. Kass

Published in: Drugs | Issue 5/2004

Abstract

Advanced glycation endproducts (AGEs) are formed by a reaction between reducing sugars and biological amines. Because of their marked stability, glycated proteins accumulate slowly over a person’s lifespan, and can contribute to age-associated structural and physiological changes in the cardiovascular system such as increased vascular and myocardial stiffness, endothelial dysfunction, altered vascular injury responses and atherosclerotic plaque formation. The mechanisms by which AGEs affect the cardiovascular system include collagen crosslinking, alteration of low-density lipoprotein molecules and impairment of cellular nitric oxide signalling through their interaction with AGE receptors (RAGEs). Thus, the accumulation of AGEs may help to explain the increased cardiac risk associated with aging as well as diabetes mellitus and hypertension, two conditions that accelerate and enhance AGE formation.

A variety of new pharmacological approaches are being developed to reduce the pathophysiological impact of AGEs. These agents can prevent AGE and AGE crosslink formation, break pre-existing AGE crosslinks, and block the interaction between AGEs and RAGEs. Such agents have been shown to reduce vascular and myocardial stiffness, inhibit atherosclerotic plaque formation and improve endothelial function in animal models. Improvement in vascular compliance has also been demonstrated with AGE crosslink breakers in clinical trials. These studies offer promise to reduce the cardiac risk associated with isolated systolic hyperten-sion, diastolic dysfunction and diabetes.

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Title: Advanced Glycation Endproduct Crosslinking in the Cardiovascular System
Potential Therapeutic Target for Cardiovascular Disease
Authors: Dr Susan J. Zieman
David A. Kass
Publication date: 01-03-2004
Publisher: Springer International Publishing
Published in: Drugs / Issue 5/2004
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200464050-00001

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Advanced Glycation Endproduct Crosslinking in the Cardiovascular System

Potential Therapeutic Target for Cardiovascular Disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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