HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolip...

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Autores principales: Mark S Borja, Lei Zhao, Bradley Hammerson, Chongren Tang, Richard Yang, Nancy Carson, Gayani Fernando, Xiaoqin Liu, Madhu S Budamagunta, Jacques Genest, Gregory C Shearer, Franck Duclos, Michael N Oda
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/1e58836a5d004ecdb31766e8e2e6b96a
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Sumario:High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.