Immunohistochemical Detection of 13(R)-hydroxyoctadecadienoic Acid in Atherosclerotic Plaques of Human Carotid Arteries Using a Novel Specific Antibody

Abstract

13-Hydroxyoctadecadienoic acid (13-HODE) is a major component of oxidized low density lipoprotein (OxLDL), which has been shown to have a crucial role in atherogenesis. Of the 13-HODE stereoisomers, 13(S)-HODE and 13(R)-HODE, little is known about the latter in contrast to the former. To detect 13(R)-HODE in atherosclerotic lesions, we prepared a mouse monoclonal antibody against 13(R)-HODE. Competitive enzyme-linked immunosorbent assay clarified the selective reaction of a clone mAb 13H1 with both free and bovine serum albumin-conjugated forms of 13(R)-HODE but not other oxidized lipids including 13(S)-HODE. Immunohistochemical analysis revealed the colocalization of 13(R)-HODE immunoreactivity with the OxLDL marker oxidized phophatidylcholine immunoreactivity in vascular endothelial cells, macrophages and migrating vascular smooth muscle cells in atherosclerotic plaques of human carotid arteries. The present results provide in vivo evidence for the formation of 13(R)-HODE in atherosclerotic lesions of carotid arteries.

Differential cell growth/apoptosis behavior of 13-hydroxyoctadecadienoic acid enantiomers in a colorectal cancer cell line

“…Although there are few studies of 13(R)-HODE biological effects, Shibata et al (43) indicate that 13(R)-HODE is a PPAR␥ agonist on the atherosclerotic plaques of human carotid arteries, thus suggesting an antiproliferative role for this metabolite. In contrast, the results given here regarding Caco-2 cell growth and DNA synthesis after incubation with 13(R)-HODE suggest that this metabolite has a significant proliferative effect in the absence of any other growth factors and show, accordingly, that 13(R)-HODE effects are PPAR␥ independent.…”

“…Moreover, we must consider that there are two stereoisomers of 13-HODE, 13-sinister-HODE [13(S)-HODE] and 13-rectus-HODE [13(R)-HODE]. While 13(S)-HODE is only produced in the metabolism of linoleic acid by 15-LOX-1 (38, 44), 13(R)-HODE can be generated by several LOXs and COXs, as well as by autooxidation processes (3,4,5,36,43).HETEs and HODES are known to modulate inflammation and may be important factors in carcinogenesis (32,38,44). In this sense, 15-LOX metabolites have been shown to play both pro-and antitumorigenic actions, whereas COX metabolites are described to be tumorigenic (42).…”

“…Moreover, we must consider that there are two stereoisomers of 13-HODE, 13-sinister-HODE [13(S)-HODE] and 13-rectus-HODE [13(R)-HODE]. While 13(S)-HODE is only produced in the metabolism of linoleic acid by 15-LOX-1 (38,44), 13(R)-HODE can be generated by several LOXs and COXs, as well as by autooxidation processes (3,4,5,36,43).…”

Oxidized metabolites of linoleic acid as biomarkers of liver injury in nonalcoholic steatohepatitis

“…The oxidized derivatives of LA (oxidized LA metabolites; OXLAMs) are mainly represented by 9- and 13-hydroxyl-octadecadienoic acid (HODE) and by the 9- and 13-oxo-octadecadienoic acid. These compounds have been demonstrated to be a major component of the oxidized [43–45] and atherosclerotic plaques [46,47]; they also play a pivotal role in the formation of foam cells, as well as in the pathogenesis of atherosclerosis [48–50]. In a recent study, OXLAM levels, in particular, 9- and 13-hydroxy-eicosatetraenoic acids, and 9- and 13-oxo-octadecadienoic acids, have been shown to be associated with NASH (but not in simple steatosis) [51].…”

Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans

“…As a major component of oxidized low-density lipoprotein (LDL) [7,10,11] and atherosclerotic plaques [12,13], OXLAMs are reported to play a central role in foam cell formation and the pathogenesis of atherosclerosis [4,8,14]. OXLAMs also can act as endogenous TRPV1 receptor channel activators (i.e.…”