title: HNE-derived 2-pentylpyrroles are generated during oxidation of LDL, are more prevalent in blood plasma from patients with renal disease or atherosclerosis, and are present in atherosclerotic plaques.
abstract: Free radical oxidation of human plasma low-density lipoprotein (LDL) produces 2-pentylpyrrole epitopes that are generated by reaction of 4-hydroxy-2-nonenal (HNE), a product of lipid oxidation, with protein lysyl residues. The HNE-derived 2-pentylpyrrole ("HNE-pyrrole") epitopes were detected with an enzyme-linked immunosorbent assay (ELISA) using antibodies (ON-KLH) raised against protein-bound 2-pentylpyrrole obtained by the reaction of 2-oxononanal (ON) with keyhole limpet hemocyanin (KLH). HNE-pyrrole epitopes in human plasma are not associated primarily with LDL protein, apolipoprotein (apo) B, since only 15% of the total HNE-pyrrole immunoreactivity is removed by immunoprecipitation of apo B. The levels of ON-KLH immunoreactivity detected in human plasma were found to be significantly elevated in renal failure and atherosclerosis patients when compared to those in healthy volunteers. HNE-pyrrole immunoreactivity was also detected in atherosclerotic plaques. The highest levels were associated with extracellular connective tissue. Levels of ON-KLH immunoreactivity in human plasma far exceed levels of free HNE, presumably because of the rapid clearance of free relative to protein-bound HNE. Therefore, HNE-pyrrole epitopes provide a more indelible marker of oxidative injury than levels of free HNE.
authors.affiliation: Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078, USA. rgs@po.cwru.edu
authors.forename: R G
authors.initials: RG
authors.lastname: Salomon
authors.forename: K
authors.initials: K
authors.lastname: Kaur
authors.forename: E
authors.initials: E
authors.lastname: Podrez
authors.forename: H F
authors.initials: HF
authors.lastname: Hoff
authors.forename: A V
authors.initials: AV
authors.lastname: Krushinsky
authors.forename: L M
authors.initials: LM
authors.lastname: Sayre
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D001161:Arteriosclerosis / Q000097:blood*; D002339:Carotid Arteries / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000097:blood*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000097:blood* / Q000737:chemistry
chemical_list: D000447:Aldehydes; D008077:Lipoproteins, LDL; D011758:Pyrroles; C099252:oxidized low density lipoprotein; C027576:4-hydroxy-2-nonenal