title: Mapping Atheroprotective Functions and Related Proteins/Lipoproteins in Size Fractionated Human Plasma.
abstract: HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS). Each fraction was evaluated for its proteomic content as well as its ability to promote cholesterol efflux and protect low density lipoprotein (LDL) from free radical oxidation. For each function, several peaks of activity were identified across the plasma size gradient. Neither cholesterol efflux or LDL antioxidation activity correlated strongly with any single protein across the fractions. However, we identified multiple proteins that had strong correlations (r values >0.7,p< 0.01) with individual peaks of activity. These proteins fell into diverse functional categories, including those traditionally associated with lipid metabolism, as well as alternative complement cascade, innate immunity and clotting cascades and immunoglobulins. Additionally, the phospholipid and cholesterol concentration of the fractions correlated strongly with cholesterol efflux (r= 0.95 and 0.82 respectively), whereas the total protein content of the fractions correlated best with antioxidant activity across all fractions (r= 0.746). Furthermore, two previously postulated subspecies (apoA-I, apoA-II and apoC-1; as well as apoA-I, apoC-I and apoJ) were found to have strong correlations with both cholesterol efflux and antioxidation activity. Up till now, very little has been known about how lipoprotein composition mediates functions like cholesterol efflux and antioxidation.
authors.affiliation: §Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.
authors.forename: Debi K
authors.initials: DK
authors.lastname: Swertfeger
authors.affiliation: §Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.
authors.forename: Hailong
authors.initials: H
authors.lastname: Li
authors.affiliation: §Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.|¶Center for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, 2120 East Galbraith Road, Cincinnati, Ohio 45237-0507.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rebholz
authors.affiliation: §Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zhu
authors.affiliation: ‖Division of Endocrinology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Shah
authors.affiliation: ¶Center for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, 2120 East Galbraith Road, Cincinnati, Ohio 45237-0507.
authors.forename: W Sean
authors.initials: WS
authors.lastname: Davidson
authors.affiliation: From the ‡School of Information Management, Wuhan University, Wuhan 430072, China; Long.Lu@cchmc.org.|§Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039.
authors.forename: Long J
authors.initials: LJ
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D002850:Chromatography, Gel; D064368:Healthy Volunteers; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010750:Phosphoproteins / Q000032:analysis / Q000097:blood*; D040901:Proteomics / Q000379:methods*; D055815:Young Adult
chemical_list: D008075:Lipoproteins, HDL; D010750:Phosphoproteins