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PMID: 2010531 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Gene expression in macrophage-rich human atherosclerotic lesions. 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts.

The Journal of clinical investigation ·Vol. 87 ·No. 4 ·1991-04-00 ·Pages 1146-52

Ylä-Herttuala S, Rosenfeld ME, Parthasarathy S, Sigal E, Särkioja T, Witztum JL, Steinberg D

Abstract

Oxidatively modified low density lipoprotein (LDL) exhibits several potentially atherogenic properties, and inhibition of LDL oxidation in rabbits decreases the rate of the development of atherosclerotic lesions. In vitro studies have suggested that cellular lipoxygenases may be involved in LDL oxidation, and we have shown previously that 15-lipoxygenase and oxidized LDL are present in rabbit atherosclerotic lesions. We now report that epitopes of oxidized LDL are also found in macrophage-rich areas of human fatty streaks as well as in more advanced human atherosclerotic lesions. Using in situ hybridization and immunostaining techniques, we also report that 15-lipoxygenase mRNA and protein colocalize to the same macrophage-rich areas. Moreover, these same lesions express abundant mRNA for the acetyl LDL receptor but no detectable mRNA for the LDL receptor. We suggest that atherogenesis in human arteries may be linked to macrophage-induced oxidative modification of LDL mediated by 15-lipoxygenase, leading to subsequent enhanced macrophage uptake, partly by way of the acetyl LDL receptor.

MeSH Terms
Arachidonate 15-Lipoxygenase/genetics Arteriosclerosis/genetics Cell Adhesion Molecules Gene Expression Humans Immunoenzyme Techniques Macrophages/physiology Muscle, Smooth, Vascular/physiology Nucleic Acid Hybridization RNA Probes RNA, Messenger/metabolism Receptors, LDL/genetics,immunology Receptors, Scavenger
Chemicals
Cell Adhesion Molecules RNA Probes RNA, Messenger Receptors, LDL Receptors, Scavenger Arachidonate 15-Lipoxygenase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ylä-Herttuala S
Department of Medicine, University of California, San Diego 92093.
Rosenfeld M E
Parthasarathy S
Sigal E
Särkioja T
Witztum J L
Steinberg D
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115111
Published
1991-04-00
Pages
1146-52
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295117
Subset
IM
Grants
NHLBI NIH HHS · HL-02047 · United States
NHLBI NIH HHS · HL-24136 · United States
NHLBI NIH HHS · NHLBI 14197 · United States
External Links
PubMed source DOI: 10.1172/JCI115111 PMC Full Text View journal details
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