PMID- 8576120
OWN - NLM
STAT- MEDLINE
DCOM- 19960311
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 3
DP  - 1996 Jan 19
TI  - Oxidation of low density lipoproteins greatly enhances their association with 
      lipoprotein lipase anchored to endothelial cell matrix.
PG  - 1329-35
AB  - Native and oxidized low density lipoprotein retention within arterial wall 
      endothelial cell matrix (ECM) is an early event in the pathogenesis of 
      atherosclerosis. Previously we showed lipoprotein lipase (LPL) addition to ECM 
      enhanced the retention of apoB-containing lipoproteins. In the present studies we 
      examined whether the oxidation of low density lipoprotein (LDL) increases its 
      retention by LPL-containing ECM. Except where noted, 125I-labeled moderately 
      oxidized LDL (ModOxLDL) was prepared by long term storage of 125I-LDL. Without 
      LPL, 125I-ModOxLDL matrix binding was low and nonsaturable. LPL preanchored to 
      ECM resulted in 125I-ModOxLDL binding that was saturable and 20-fold greater than 
      in the absence of LPL, with an association constant equal to 2.6 nM. 
      Copper-oxidized LDL (Cu-OxLDL) was able to compete with 125I-ModOxLDL, whereas a 
      60-fold native LDL excess had no effect. Reconstituted apolipoprotein B from 
      Cu-OxLDL also reduced 125I-ModOxLDL to LPL, whereas liposomes derived from the 
      lipid extract of Cu-OxLDL had no effect on binding. These data suggest that the 
      increased binding of oxidized LDL to LPL-ECM may be due to the exposure of novel 
      apoB binding sites and not an oxidized lipid moiety. 125I-ModOxLDL binding was 
      also not affected by either preincubation with a 300-fold molar excess of 
      apoE-poor HDL or an 340-fold molar excess of Cu-Ox-HDL. In contrast, a 4-fold 
      apoE-rich HDL excess (based on protein) totally inhibited 125I-ModOxLDL matrix 
      retention. Positively charged peptides of polyarginine mimicked the effect of 
      apoE-rich HDL in reducing the 125I-ModOxLDL retention; however, polylysine had no 
      effect. We postulate that the oxidation of LDL may be a mechanism that enhances 
      LDL retention by the ECM-bound LPL and that the protective effects of 
      apoE-containing HDL may in part be due to its ability to block the retention of 
      oxidized LDL in vivo.
FAU - Auerbach, B J
AU  - Auerbach BJ
AD  - Atherosclerosis Therapeutics Parke-Davis Pharmaceutical Research, Division of 
      Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
FAU - Bisgaier, C L
AU  - Bisgaier CL
FAU - Wolle, J
AU  - Wolle J
FAU - Saxena, U
AU  - Saxena U
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Apolipoproteins E)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Lipoproteins, LDL)
RN  - 789U1901C5 (Copper)
RN  - EC 3.1.1.34 (Lipoprotein Lipase)
SB  - IM
MH  - Animals
MH  - Aorta
MH  - Apolipoproteins E/pharmacology
MH  - Cattle
MH  - Cells, Cultured
MH  - Copper/pharmacology
MH  - Electrophoresis, Agar Gel
MH  - Endothelium, Vascular/*metabolism
MH  - Extracellular Matrix/drug effects/*metabolism
MH  - Female
MH  - Humans
MH  - Kinetics
MH  - Lipoprotein Lipase/*metabolism
MH  - Lipoproteins, HDL/blood/isolation & purification/pharmacology
MH  - Lipoproteins, LDL/blood/isolation & purification/*metabolism
MH  - Milk/enzymology
MH  - Oxidation-Reduction
MH  - Protein Binding
EDAT- 1996/01/19 00:00
MHDA- 1996/01/19 00:01
CRDT- 1996/01/19 00:00
PHST- 1996/01/19 00:00 [pubmed]
PHST- 1996/01/19 00:01 [medline]
PHST- 1996/01/19 00:00 [entrez]
AID - S0021-9258(17)44931-3 [pii]
AID - 10.1074/jbc.271.3.1329 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Jan 19;271(3):1329-35. doi: 10.1074/jbc.271.3.1329.