Journal
JOURNAL OF LIPID RESEARCH
Volume 61, Issue 6, Pages 816-829Publisher
ELSEVIER
DOI: 10.1194/jlr.RA119000312
Keywords
atherosclerosis; oxidized low density lipoprotein; oxidized high density lipoprotein; apolipoproteins; proteomics; lipidomics; high density lipoprotein
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Funding
- Japan Society for the Promotion of Science KAKENHI [JP15K07944, JP21790092, JP24590094, JP24790087]
- Private University Research Branding Project
- Strategic Research Foundation at Private Universities [S1001011]
- Showa University
- Japan Science Society Sasakawa Scientific Research Grant [22-418]
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Oxidized LDL (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(-)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(-) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues identified in apoB. The amount of oxPC adducts of apoB was higher in the LDL(-) than in the L1 fraction, as determined using Western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC mAb. The majority of PC species were not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.
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