TY - JOUR
T1 - Role of oxidatively modified LDL in atherosclerosis
AU - Steinbrecher, Urs P.
AU - Zhang, Hanfang
AU - Lougheed, Marilee
N1 - Funding Information:
Acknowledgements--The authors are Indebted to many colleagues and collaborators for stimulating discussions and advice, but wish to express particular appreciation to Drs Joseph L Witztum, Alan Chalt, Guy Chlsolm, Alan Attle, Sampath Parthasarathy. Michael Rosenfeld, Margaret Haberland, and Daniel Steinberg Studies from our laboratory were supported by grants from the Medical Research Council of Canada, the B C Y Heart Foundation, and the B C Health Care Research Foundation
PY - 1990
Y1 - 1990
N2 - Oxidative modification of LDL is accompanied by a number of compositional and structural changes, including increased electrophoretic mobility, increased density, fragmentation of apolipoprotein B, hydrolysis of phosphatidylcholine, derivatization of lysine amino groups, and generation of lfuorescent adducts due to covalent binding of lipid oxidation products to apo B. In addition, oxidation of LDL has been shown to result in numerous changes in its biologic properties that could have pathogenetic imortance, including accelerated uptake in macrophages, cytotoxicity, and chemotactic activity for monocytes. The present article summarrizes very recent developments related to the mechanism of oxidation of LDL by cells, receptor-mediated uptake of oxidized LDL in macrophages, the mechanism of phosphatidylcholine hydrolysis during LDL oxidation, and other biologic actions of oxidized LDL including cytotoxicity, altered eicosanoid metabolism, and effects on the secretion of growth factors and chemotactic factors. In addition, this review will exzmine the evidence for the presence of oxidized LDL in vivo and the evidence that oxidized LDL plays a pathogenetic role in atherosclerosis.
AB - Oxidative modification of LDL is accompanied by a number of compositional and structural changes, including increased electrophoretic mobility, increased density, fragmentation of apolipoprotein B, hydrolysis of phosphatidylcholine, derivatization of lysine amino groups, and generation of lfuorescent adducts due to covalent binding of lipid oxidation products to apo B. In addition, oxidation of LDL has been shown to result in numerous changes in its biologic properties that could have pathogenetic imortance, including accelerated uptake in macrophages, cytotoxicity, and chemotactic activity for monocytes. The present article summarrizes very recent developments related to the mechanism of oxidation of LDL by cells, receptor-mediated uptake of oxidized LDL in macrophages, the mechanism of phosphatidylcholine hydrolysis during LDL oxidation, and other biologic actions of oxidized LDL including cytotoxicity, altered eicosanoid metabolism, and effects on the secretion of growth factors and chemotactic factors. In addition, this review will exzmine the evidence for the presence of oxidized LDL in vivo and the evidence that oxidized LDL plays a pathogenetic role in atherosclerosis.
KW - Aterosclerosis
KW - Free radicals
KW - Lipid peroxidation
KW - Macrophages
KW - Oxidized LDL
KW - Scavenger receptor
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U2 - 10.1016/0891-5849(90)90119-4
DO - 10.1016/0891-5849(90)90119-4
M3 - Article
C2 - 2227530
AN - SCOPUS:0024992023
SN - 0891-5849
VL - 9
SP - 155
EP - 168
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 2
ER -