Chemistry Commons^™

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%) …