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Function And Distribution Of Apolipoprotein A1 In The Artery Wall Are Markedly Distinct From Those In Plasma, Joseph A. Didonato, Ying Huang, Kulwant S. Aulak, Orli Even-Or, Gary Gerstenecker, Valentin Gogonea, Yuping Wu, Paul L. Fox, W.H. Wilson Tang, Edward F. Plow, Jonathan D. Smith, Edward A. Fisher, Stanley L. Hazen
Function And Distribution Of Apolipoprotein A1 In The Artery Wall Are Markedly Distinct From Those In Plasma, Joseph A. Didonato, Ying Huang, Kulwant S. Aulak, Orli Even-Or, Gary Gerstenecker, Valentin Gogonea, Yuping Wu, Paul L. Fox, W.H. Wilson Tang, Edward F. Plow, Jonathan D. Smith, Edward A. Fisher, Stanley L. Hazen
Chemistry Faculty Publications
Background—Prior studies show that apolipoprotein A1 (apoA1) recovered from human atherosclerotic lesions is highly oxidized. Ex vivo oxidation of apoA1 or high-density lipoprotein (HDL) cross-links apoA1 and impairs lipid binding, cholesterol efflux, and lecithin-cholesterol acyltransferase activities of the lipoprotein. Remarkably, no studies to date directly quantify either the function or HDL particle distribution of apoA1 recovered from the human artery wall. Methods and Results—A monoclonal antibody (10G1.5) was developed that equally recognizes lipid-free and HDL-associated apoA1 in both native and oxidized forms. Examination of homogenates of atherosclerotic plaque–laden aorta showed >100-fold enrichment of apoA1 compared with normal aorta (P<0.001). Surprisingly, buoyant density fractionation revealed that only a minority (<3% of total) of apoA1 recovered from either lesions or normal aorta resides within an HDL-like particle (1.063≤d≤1.21). In contrast, the majority (>90%) …
The Low-Resolution Structure Of Nascent High Density Lipoprotein Reconstituted With Dmpc With And Without Cholesterol Reveals A Mechanism For Particle Expansion, Valentin Gogonea, Gary S. Gerstenecker, Zhiping Wu, Xavier Lee, Celalettin Topbas, Matthew A. Wagner, Thomas C. Tallant, Jonathan D. Smith, Phil Callow, Vitaliy Pipich, Helen Malet, Guy Schoehn, Joseph A. Didonato, Stanley L. Hazen
The Low-Resolution Structure Of Nascent High Density Lipoprotein Reconstituted With Dmpc With And Without Cholesterol Reveals A Mechanism For Particle Expansion, Valentin Gogonea, Gary S. Gerstenecker, Zhiping Wu, Xavier Lee, Celalettin Topbas, Matthew A. Wagner, Thomas C. Tallant, Jonathan D. Smith, Phil Callow, Vitaliy Pipich, Helen Malet, Guy Schoehn, Joseph A. Didonato, Stanley L. Hazen
Chemistry Faculty Publications
High density lipoproteins (HDL) are athero-protective particles under investigation as potential therapeutic agents for cardiovascular disease. We applied small angle neutron scattering (SANS) with contrast variation to obtain the low resolution structure of nascent HDL (nHDL) reconstituted with dimyristoyl phosphatidyl choline (DMPC), apoA1:DMPC (1:80, mol:mol). The overall shape of the entire particle is discoidal, with low resolution architecture of apoA1 visualized as an open, contorted, and slightly out of plane structure with three arms, while the low resolution shape of the lipid phase is an oblate ellipsoid that fits well within the protein shape. Modeling studies incorporating the SANS data …