High-Density Lipoproteins Inhibit Cytokine-Induced Expression of Endothelial Cell Adhesion Molecules

Cockerill, Gillian; Rye, Kerry‐Anne; Gamble, Jennifer R.; Vadas, Mathew A.; Barter, Philip J.

doi:10.1161/01.atv.15.11.1987

Cited by 705 publications

(477 citation statements)

References 39 publications

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“…HDL has been demonstrated in vitro to decrease neutrophil degranulation and superoxide production, 32 inhibit LDL oxidation, 33 protect endothelial cells against the effects of oxidized LDL, 34 and prevent the cytokine-induced upregulation of adhesion molecules on endothelial cells, 35 effects that have not been demonstrated to be specifically due to the apoA-I component of the HDL particle. HDL contains a variety of proteins in addition to apoA-I that have been shown to be antiatherogenic in vivo, including apoE, 19,20 apoA-IV, 21,22 LCAT, 23 CETP, 24 and paraoxonase.…”

Section: Discussionmentioning

confidence: 99%

Regression of Atherosclerosis Induced by Liver-Directed Gene Transfer of Apolipoprotein A-I in Mice

et al. 1999

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Background-The ability of apolipoprotein (apo)A-I to induce regression of preexisting atherosclerotic lesions has not been determined, and a mouse model of atherosclerosis regression has not yet been reported. Methods and Results-LDL receptor-deficient mice were fed a western-type diet for 5 weeks to induce atherosclerotic lesions. A second-generation recombinant adenovirus encoding human apoA-I or a control adenovirus were injected intravenously in order to express apoA-I in the liver. Three days after injection, total apoA-I levels in mice injected with the apoA-I-expressing adenovirus were 216Ϯ16.0 mg/dL, compared with 68.0Ϯ3.0 mg/dL in control virus-injected mice (PϽ0.001). HDL cholesterol levels in mice injected with the AdhapoA-I vector 7 days after injection were 189Ϯ21.0 mg/dL, compared with 123Ϯ8.0 mg/dL in control virus-injected mice (PϽ0.02). Total and non-HDL cholesterol levels did not differ between the 2 groups. Atherosclerotic lesion area was quantified by en face analysis of the aorta and cross-sectional analysis of the aortic root. Compared with baseline mice, atherosclerosis progressed in mice injected with the control adenovirus. In contrast, in mice expressing apoA-I compared with baseline mice, total en face aortic lesion area was reduced by 70% and aortic root lesion was reduced by 46%. Expression of apoA-I was associated with a significant reduction in the fraction of lesions occupied by macrophages and macrophage-derived foam cells. Conclusions-Liver-directed gene transfer of human apoA-I resulted in significant regression of preexisting atherosclerotic lesions in LDL receptor-deficient mice as assessed by 2 independent methods. (Circulation. 1999;100:1816-1822.)

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Section: Discussionmentioning

confidence: 99%

Regression of Atherosclerosis Induced by Liver-Directed Gene Transfer of Apolipoprotein A-I in Mice

et al. 1999

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“…28,43 ApoE-deficient mice lacking the macrophage scavenger receptor A had a 58% decrease in atherosclerosis. 44 The vascular wall is implicated in studies using cultured endothelial and/or smooth muscle cells, which suggests that differences in lipoprotein retention, 45 adhesion molecule expression, 46 and subendothelial matrix components 47,48 would be likely to affect foam cell lesion formation.…”

Section: Discussionmentioning

confidence: 99%

Genetic Background Determines the Extent of Atherosclerosis in ApoE-Deficient Mice

Dansky

Charlton

Sikes

et al. 1999

ATVB

151

135

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Abstract-Two strains of ApoE-deficient mice were found to have markedly different plasma lipoprotein profiles and susceptibility to atherosclerosis when fed either a low-fat chow or a high-fat Western-type diet. FVB/NJ ApoE-deficient (FVB E0) mice had higher total cholesterol, HDL cholesterol, ApoA1, and ApoA2 levels when compared with C57BL/6J ApoE-deficient (C57 E0) mice. At 16 weeks of age, mean aortic root atherosclerotic lesion area was 7-to 9-fold higher in chow diet-fed C57 E0 mice and 3.5-fold higher in Western diet-fed C57 E0 mice compared with FVB E0 mice fed similar diets. Lesion area in chow diet-fed first-generation mice from a strain intercross was intermediate in size compared with parental values. The distribution of the lesion area in 150 chow diet-fed second-generation progeny spanned the range of the lesion area in both parental strains. There were no correlations between total cholesterol, non-HDL cholesterol, HDL cholesterol, ApoA1, ApoA2, ApoJ, or anti-cardiolipin antibodies and lesion area in the second-generation progeny. Thus, a genomic approach may succeed in identifying the genes responsible for the variation in atherosclerosis susceptibility in these 2 strains of ApoE-deficient mice, which could not be explained by measured plasma parameters.

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“…The results of our study, which show that patients with increased levels of triglycerides and low HDL cholesterol have increased levels of sCAMs, are consistent with previous in vitro studies showing that oxidized fatty acids increase endothelial expression of CAMs in response to cytokines, whereas high levels of HDL inhibit the endothelial expression of CAMs in response to cytokines. 9 Omacor contains 3.3 IU/g of vitamin E, which may have prevented the enhanced oxidation of fatty acids seen in some studies with fish oils. 23 These data suggest that increased expression of CAMs may be a mechanism by which high triglyceride/low HDL promotes atherogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro studies have shown that low HDL and oxidized fatty acids increase the endothelial expression of CAMs in response to cytokines. [6][7][8][9] Assessment of the relationship between elevated triglycerides/low HDL and the expression of CAMs in humans has been hampered by the difficulty of quantitative assessment of CAM expression in vivo.…”

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confidence: 99%

Soluble Cell Adhesion Molecules in Hypertriglyceridemia and Potential Significance on Monocyte Adhesion

Abe

El-Masri

Kimball

et al. 1998

ATVB

199

145

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Abstract-Hypertriglyceridemia may contribute to the development of atherosclerosis by increasing expression of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as markers for CAMs. In this study, we examined the association between sCAMs and other risk factors occurring with hypertriglyceridemia, the effect of triglyceride reduction on sCAM levels, and the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in monocyte adhesion in vitro. Compared with normal control subjects (nϭ20), patients with hypertriglyceridemia and low HDL (nϭ39) had significantly increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) (316Ϯ28.8 versus 225Ϯ16.6 ng/mL), sVCAM-1 (743Ϯ52.2 versus 522Ϯ43.6 ng/mL), and soluble E-selectin (83Ϯ5.9 versus 49Ϯ3.6 ng/mL). ANCOVA showed that the higher sCAM levels in patients occurred independently of diabetes mellitus and other risk factors. In 27 patients who received purified n-3 fatty acid (Omacor) 4 g/d for Ն7 months, triglyceride level was reduced by 47Ϯ4.6%, sICAM-1 level was reduced by 9Ϯ3.4% (Pϭ.02), and soluble E-selectin level was reduced by 16Ϯ3.2% (PϽ.0001), with the greatest reduction in diabetic patients. These results support previous in vitro data showing that disorders in triglyceride and HDL metabolism influence CAM expression and treatment with fish oils may alter vascular cell activation. In a parallel-plate flow chamber, recombinant sVCAM-1 at the concentration seen in patients significantly inhibited adhesion of monocytes to interleukin-

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High-Density Lipoproteins Inhibit Cytokine-Induced Expression of Endothelial Cell Adhesion Molecules

Cited by 705 publications

References 39 publications

Regression of Atherosclerosis Induced by Liver-Directed Gene Transfer of Apolipoprotein A-I in Mice

Regression of Atherosclerosis Induced by Liver-Directed Gene Transfer of Apolipoprotein A-I in Mice

Genetic Background Determines the Extent of Atherosclerosis in ApoE-Deficient Mice

Soluble Cell Adhesion Molecules in Hypertriglyceridemia and Potential Significance on Monocyte Adhesion

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