Impact of plasma oxidized low-density lipoprotein removal on atherosclerosis

Yasushi Ishigaki, Hideki Katagiri, Junhong Gao, Tetsuya Yamada, Junta Imai, Kenji Uno, Yutaka Hasegawa, Keizo Kaneko, Takehide Ogihara, Hisamitsu Ishihara, Yuko Sato, Kenji Takikawa, Norihisa Nishimichi, Haruo Matsuda, Tatsuya Sawamura, Yoshitomo Oka

研究成果: Article査読

139 被引用数 (Scopus)

抄録

Background - Several clinical studies of statin therapy have demonstrated that lowering low-density lipoprotein (LDL) cholesterol prevents atherosclerotic progression and decreases cardiovascular mortality. In addition, oxidized LDL (oxLDL) is suggested to play roles in the formation and progression of atherosclerosis. However, whether lowering oxLDL alone rather than total LDL, affects atherogenesis remains unclear. Methods and results - To clarify the atherogenic impact of oxLDL, lectin-like oxLDL receptor 1 (LOX-1), an oxLDL receptor, was expressed ectopically in the liver with adenovirus administration in apolipoprotein E-deficient mice at 46 weeks of age. Hepatic LOX-1 expression enhanced hepatic oxLDL uptake, indicating functional expression of LOX-1 in the liver. Although plasma total cholesterol, triglyceride, and LDL cholesterol levels were unaffected, plasma oxLDL was markedly and transiently decreased in LOX-1 mice. In controls, atherosclerotic lesions, detected by Oil Red O staining, were markedly increased (by 38%) during the 4-week period after adenoviral administration. In contrast, atherosclerotic progression was almost completely inhibited by hepatic LOX-1 expression. In addition, plasma monocyte chemotactic protein-1 and lipid peroxide levels were decreased, whereas adiponectin was increased, suggesting decreased systemic oxidative stress. Thus, LOX1 expressed in the livers of apolipoprotein E-deficient mice transiently removes oxLDL from circulating blood and possibly decreases systemic oxidative stress, resulting in complete prevention of atherosclerotic progression despite the persistence of severe LDL hypercholesterolemia and hypertriglyceridemia. Conlusions - OxLDL has a major atherogenic impact, and oxLDL removal is a promising therapeutic strategy against atherosclerosis.

本文言語English
ページ(範囲)75-83
ページ数9
ジャーナルCirculation
118
1
DOI
出版ステータスPublished - 2008 7 1

ASJC Scopus subject areas

  • 循環器および心血管医学
  • 生理学(医学)

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