title: Function and distribution of apolipoprotein A1 in the artery wall are markedly distinct from those in plasma.
abstract: 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.
  
  
  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%) of apoA1 within aortic tissue (normal and lesions) was recovered within the lipoprotein-depleted fraction (d>1.21). Moreover, both lesion and normal artery wall apoA1 are highly cross-linked (50% to 70% of total), and functional characterization of apoA1 quantitatively recovered from aorta with the use of monoclonal antibody 10G1.5 showed ≈80% lower cholesterol efflux activity and ≈90% lower lecithin-cholesterol acyltransferase activity relative to circulating apoA1.
  
  
  CONCLUSIONS
  The function and distribution of apoA1 in human aorta are quite distinct from those found in plasma. The lipoprotein is markedly enriched within atherosclerotic plaque, predominantly lipid-poor, not associated with HDL, extensively oxidatively cross-linked, and functionally impaired.
authors: Departments of Cellular and Molecular Medicine, Lerner Research Institute (J.A.D., Y.H., K.A., G.G., V.G., P.L.F., W.H.W.T., J.D.S., S.L.H.), Cardiovascular Medicine, Heart, and Vascular Institute (W.H.W.T., J.D.S., S.L.H.), and Molecular Cardiology, Lerner Research Institute (E.F.P.), Cleveland Clinic, Cleveland, OH; Department of Medicine, New York University, New York, NY (O.E.-O., E.A.F.); and Departments of Chemistry (G.G., V.G., S.L.H.) and Mathematics (Y.W.), Cleveland State University, Cleveland, OH.
authors: Joseph A
authors: JA
authors: DiDonato
authors: Ying
authors: Y
authors: Huang
authors: Kulwant S
authors: KS
authors: Aulak
authors: Orli
authors: O
authors: Even-Or
authors: Gary
authors: G
authors: Gerstenecker
authors: Valentin
authors: V
authors: Gogonea
authors: Yuping
authors: Y
authors: Wu
authors: Paul L
authors: PL
authors: Fox
authors: W H Wilson
authors: WH
authors: Tang
authors: Edward F
authors: EF
authors: Plow
authors: Jonathan D
authors: JD
authors: Smith
authors: Edward A
authors: EA
authors: Fisher
authors: Stanley L
authors: SL
authors: Hazen
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001011:Aorta / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D050197:Atherosclerosis / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D058226:Plaque, Atherosclerotic / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase
keywords: apolipoproteins; arteriosclerosis; cardiovascular diseases; plaque, atherosclerotic
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