Abstract | BACKGROUND: 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. CONCLUSIONS:
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Authors | 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 |
Journal | Circulation
(Circulation)
Vol. 118
Issue 1
Pg. 75-83
(Jul 01 2008)
ISSN: 1524-4539 [Electronic] United States |
PMID | 18559699
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adiponectin
- Apolipoproteins E
- Lipid Peroxides
- Lipoproteins, LDL
- Olr1 protein, mouse
- Receptors, Oxidized LDL
- Scavenger Receptors, Class E
- oxidized low density lipoprotein
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Topics |
- Adenoviridae
(genetics)
- Adiponectin
(metabolism)
- Animals
- Apolipoproteins E
(deficiency)
- Atherosclerosis
(blood, genetics, prevention & control)
- Disease Models, Animal
- Genetic Therapy
(methods)
- Lipid Peroxides
(metabolism)
- Lipoproteins, LDL
(blood, metabolism)
- Liver
(metabolism, virology)
- Mice
- Mice, Knockout
- Oxidative Stress
(drug effects)
- Receptors, Oxidized LDL
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Scavenger Receptors, Class E
(genetics, metabolism)
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