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Low density lipoprotein undergoes oxidative modification in vivo.
W Palinski1, M E Rosenfeld, S Ylä-Herttuala
1Department of Medicine, University of California, San Diego, La Jolla 92093.
Summary
Oxidized low-density lipoprotein (LDL) is crucial in atherosclerosis development. This study provides evidence of LDL oxidation in vivo, identifying oxidized LDL and related antibodies in atherosclerotic lesions.
Area of Science:
- Cardiovascular biology
- Lipid metabolism
- Immunology
Background:
- Atherosclerosis pathogenesis involves foam cell formation.
- Oxidative modification of low-density lipoprotein (LDL) is hypothesized to precede foam cell development.
- Oxidized LDL may form conjugates with apolipoprotein B.
Purpose of the Study:
- To investigate the presence and significance of oxidized LDL in vivo.
- To gather evidence supporting the role of LDL oxidation in atherosclerosis.
Main Methods:
- Immunohistochemical analysis of atherosclerotic lesions using antibodies against oxidized LDL and its specific epitopes (malondialdehyde-lysine, 4-hydroxynonenal-lysine).
- Extraction and characterization of LDL from atherosclerotic lesions.
- Detection of autoantibodies against malondialdehyde-conjugated LDL in serum samples.
Main Results:
- Antibodies against oxidized LDL and specific oxidized epitopes recognized materials within atherosclerotic lesions of LDL receptor-deficient rabbits.
- LDL isolated from these lesions was recognized by an antiserum specific for malondialdehyde-conjugated LDL.
- Elevated titers of autoantibodies against malondialdehyde-LDL were detected in both rabbit and human sera.
Conclusions:
- The findings provide strong evidence for LDL oxidation occurring in vivo.
- Oxidized LDL and associated autoantibodies are present in atherosclerotic lesions and circulation.
- This supports the hypothesis that oxidized LDL plays a key role in the development of atherosclerosis.