title: HDL-apoA-I exchange: rapid detection and association with atherosclerosis.
abstract: 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.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Borja
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Bradley
authors.initials: B
authors.lastname: Hammerson
authors.forename: Chongren
authors.initials: C
authors.lastname: Tang
authors.forename: Richard
authors.initials: R
authors.lastname: Yang
authors.forename: Nancy
authors.initials: N
authors.lastname: Carson
authors.forename: Gayani
authors.initials: G
authors.lastname: Fernando
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Liu
authors.forename: Madhu S
authors.initials: MS
authors.lastname: Budamagunta
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Shearer
authors.forename: Franck
authors.initials: F
authors.lastname: Duclos
authors.forename: Michael N
authors.initials: MN
authors.lastname: Oda
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood; D000328:Adult; D000368:Aged; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood* / Q000737:chemistry; D050197:Atherosclerosis / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry; D011485:Protein Binding; D011817:Rabbits; D012307:Risk Factors; D055815:Young Adult
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D016877:Oxidants; D006861:Hydrogen Peroxide; D009195:Peroxidase