Paradoxical increase in LDL oxidation by endothelial cells from an atherosclerosis-resistant mouse strain

Toru Miyoshi, Alan H. Matsumoto, Weibin Shi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Oxidative modification of LDL accumulated in the subendothelial space is a critical step in atherogenesis. Mouse strains C57BL/6 (B6) and BALB/c differ markedly in atherosclerosis susceptibility. We sought to determine whether variation of endothelial cells in the capacity to oxidize LDL or in response to minimally modified LDL (MM-LDL) constitutes a genetic component in atherosclerosis. LDL oxidation was assessed by measuring thiobarbituric acid-reactive substance (TBARS) production. Responses to MM-LDL were evaluated by examining induction of monocyte chemotactic protein-1, macrophage-colony stimulating factor, and vascular cell adhesion molecule-1. Both strains exhibited comparable endothelial responses to MM-LDL, whereas BALB/c mice had an increased rate of oxidizing LDL compared with B6 mice. To examine whether endothelial nitric oxide synthase (eNOS) contributed to the difference in LDL oxidation, cells were incubated with native LDL in the presence or absence of NΩ-nitro-l-arginine methyl ester (l-NAME), a specific NOS inhibitor. Although l-NAME significantly inhibited endothelial cell-mediated LDL oxidation, it failed to abolish the difference between the strains. In contrast, Baicalein, a specific 12/15 lipoxygenase inhibitor, abolished the difference in LDL oxidation. Thus, the paradoxical increase in LDL oxidation by endothelial cells is attributable to higher oxidant activity of 12/15-lipoxygenase in BALB/c mice and endothelial cells appear unlikely to be a source of the resistance to atherosclerosis.

Original languageEnglish
Pages (from-to)259-265
Number of pages7
JournalAtherosclerosis
Volume192
Issue number2
DOIs
Publication statusPublished - Jun 1 2007
Externally publishedYes

Keywords

  • Atherosclerosis
  • Endothelium
  • Lipoproteins
  • Mouse
  • Peroxidation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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