Advanced glycation end product cross-linking: pathophysiologic role and therapeutic target in cardiovascular disease.
Advanced glycation end products (AGEs) form by a nonenzymatic reaction between reducing sugars and biological proteins. These stable compounds accumulate slowly throughout the life span and contribute to structural and physiologic changes in the cardiovascular system such as increased vascular and myocardial stiffness, endothelial dysfunction, altered vascular injury responses, and atherosclerotic plaque formation. Mechanisms underlying these alterations include AGE cross-linking of collagen and AGE interactions with circulating proteins and AGE receptors. The clinical manifestations of AGE accrual-isolated systolic hypertension, endothelial and diastolic dysfunction, and atherosclerosis-underscore their role in increased cardiovascular risk associated with aging as well as diabetes and hypertension, conditions that enhance AGE formation. New pharmacologic agents that prevent AGE, break cross-links, or block AGE receptors reduce vascular and myocardial stiffness, inhibit atherosclerotic plaque formation, and improve endothelial function. These agents promise to reduce the risk of isolated systolic hypertension, diastolic dysfunction, and diabetes, and thus, heart failure.
Zieman
Susan
S
Johns Hopkins Medical Institutions, Baltimore, MD, USA. szieman@jhmi.edu
Kass
David
D
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000276:immunology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000276:immunology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism / Q000627:therapeutic use; D012307:Risk Factors
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D003094:Collagen