In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid

Yamada, Hideto; Yoshida, Masayuki; Nakano, Yasutaka; Suganami, Takayoshi; Satoh, Noriko; Mita, Tomoya; Azuma, Kosuke; Ichii, Michiko; Yamamoto, Yukio; Kamei, Yasutomi; Horie, Minoru; Watada, Hirotaka; Ogawa, Yoshihiro

doi:10.1161/atvbaha.108.171736

Cited by 98 publications

(72 citation statements)

References 40 publications

(33 reference statements)

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“…7A). These findings EPA is administered to metabolic syndrome patients, the plasma levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) decrease 23) . Some clinical studies have reported that PTX3, a vascular-specific inflammatory marker associated with atherosclerosis and ischemic heart disease, shows a negative correlation with blood EPA levels 24) .…”

Section: Discussionmentioning

confidence: 83%

Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase

Ishida

Naoe

Nakakuki

et al. 2015

JAT

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Aim: Vascular endothelial dysfunction is considered an early predictor of atherosclerosis. It has been proven that elevated blood levels of free fatty acids pose a substantial risk for the development of cardiovascular disease. In this study, we examined the effects of palmitic acid (PA), a saturated fatty acid, on endothelial function by using the expression of adhesion molecule, cytokines, and inflammatory protein as indicators, as well as investigated the effects of eicosapentaenoic acid, an n-3 polyunsaturated fatty acid. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to PA and EPA. Results: When HUVEC were exposed to PA, there was an increase in the expression of adhesion molecule, cytokines, and inflammatory protein (ICAM-1, MCP-1, interleukin-6, PTX3). PA augmented the expression of long-chain acyl-CoA synthetase (ACSL) and the cyclin-dependent kinase inhibitor p21, and enhanced the phosphorylation of p65, a component of NF-B. ACSL inhibition and siRNA-mediated ACSL3 knockdown suppressed the PA-induced increase in the expression of adhesion molecule, cytokines, and inflammatory protein, and ACSL inhibition suppressed the enhancement of p65 phosphorylation. In addition, p21 knockdown suppressed the PA-induced increase in the expression of MCP-1 and ICAM-1. EPA suppressed the PA-induced increase in the expression of ACSL and p21, the enhancement of p65 phosphorylation, as well as the associated increase in the expression of ICAM-1, MCP-1, interleukin-6, and PTX3. Conclusions: These results suggest that the ACSL, p21, and NF-B-dependent pathway may possibly be involved in PA-induced vascular endothelial dysfunction, and that EPA ameliorates this at least in part through the regulation of ACSL3 expression.

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Section: Discussionmentioning

confidence: 83%

Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase

Ishida

Naoe

Nakakuki

et al. 2015

JAT

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“…We recently demonstrated that treatment with highly purified EPA decreased the small-dense LDL, oxidized LDL, high-sensitivity C-reactive protein (CRP) and the cardio-ankle vascular index (CAVI), a new index of arterial stiffness not influenced by the blood pressure, and increased the adiponectin level in obese Japanese patients. All of these effects of EPA may contribute to cardioprotection in patients with obesity and metabolic syndrome [7][8][9][10] . It has been reported that n-3 PUFAs, including EPA and docosahexaenoic acid (DHA), exert antiplatelet and anti-inflammatory actions, in part through antagonizing the activity of proinflammatory eicosanoids derived from arachidonic acid (AA), one of the n-6 PUFAs 5,11) .…”

Section: Study Protocolmentioning

confidence: 99%

An Increase in the EPA/AA Ratio is Associated with Improved Arterial Stiffness in Obese Patients with Dyslipidemia

Itô

Satoh‐Asahara

Yamakage

et al. 2014

JAT

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Aim: Previous epidemiological studies demonstrated that the ratio of n-6 to n-3 polyunsaturated fatty acids is associated with cardiovascular diseases. We herein investigated whether the beneficial effect of highly purified eicosapentaenoic acid (EPA) on arterial stiffness is associated with changes in the ratio of polyunsaturated fatty acids, such as EPA, docosahexaenoic acid (DHA) and dihomo-γ-linolenic acid (DGLA), relative to arachidonic acid (AA), in obese Japanese patients with dyslipidemia. Methods: The EPA/AA, DHA/AA and DGLA/AA ratios were compared between obese patients with (n=94) and without (n= 31) dyslipidemia. Among the former group, 88 patients received either highly purified EPA treatment (1.8 g daily, n = 45) or treatment without EPA (control, n = 43). Results: At baseline, the ratios of DHA/AA and DGLA/AA were significantly (P＜0.05) higher in obese patients with dyslipidemia than in those without, while the EPA/AA ratio was similar between patients with and without dyslipidemia. EPA significantly reduced the hemoglobin A1c, total cholesterol, triglycerides, CRP, cardio-ankle vascular index (CAVI) (an index of arterial stiffness) and the DGLA/AA ratio relative to the control at three months after the treatment. On the other hand, EPA significantly increased the adiponectin level and EPA/AA ratio (P＜0.05). A multivariate regression analysis revealed that only age, an increase in the EPA/AA ratio and a decrease in the CRP level were significant determinants of a reduction of the CAVI by EPA. Conclusion: These findings suggest that EPA improves the arterial stiffness in association with an increase in the EPA/AA ratio and a decrease in inflammation in obese patients with dyslipidemia. J Atheroscler Thromb, 2014; 21:248-260.

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“…In EPA-treated mice, the vascular cell adhesion molecule-1 (VCAM-1) expression in endothelial cells is controlled, and monocyte adhesion to the endothelium is reduced. The administration of hp-EPA-E (Epadel ® , 1.8 g/day) in patients with metabolic syndrome significantly decreases the blood levels of VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) 81) . The addition of EPA or DHA to endothelial cells inhibits the increased expression of adhesive factors (ICAM-1, VCAM-1 and E-selectin) induced by interleukin 1β 82) .…”

Section: Effects Of Pgi2 and Pgi3 On Neoangiogenesismentioning

confidence: 99%

Eicosapentaenoic Acid (EPA) Reduces Cardiovascular Events: Relationship with the EPA/Arachidonic Acid Ratio

Ohnishi

Saitō

2013

JAT

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The clinical efficacy of fish oil and high-purity eicosapentaenoic acid ethyl ester (hp-EPA-E) for treating cardiovascular disease (CVD) has been reported. Fish oil contains saturated and monounsaturated fatty acids that have pharmacological effects opposite to those of ω3 fatty acids (ω3). Moreover, ω3, such as EPA and docosahexaenoic acid (DHA), do not necessarily have the same metabolic and biological actions. This has obscured the clinical efficacy of ω3. Recently, the Japan EPA Lipid Intervention Study (JELIS) of hp-EPA-E established the clinical efficacy of EPA for CVD, and higher levels of blood EPA, not DHA, were found to be associated with a lower incidence of major coronary events. A significant reduction in the risk of coronary events was observed when the ratio of EPA to arachidonic acid (AA) (EPA/AA) was ＞0.75. Furthermore, the ratio of prostaglandin (

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In Vivo and In Vitro Inhibition of Monocyte Adhesion to Endothelial Cells and Endothelial Adhesion Molecules by Eicosapentaenoic Acid

Cited by 98 publications

References 40 publications

Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase

Eicosapentaenoic Acid Prevents Saturated Fatty Acid-Induced Vascular Endothelial Dysfunction: Involvement of Long-Chain Acyl-CoA Synthetase

An Increase in the EPA/AA Ratio is Associated with Improved Arterial Stiffness in Obese Patients with Dyslipidemia

Eicosapentaenoic Acid (EPA) Reduces Cardiovascular Events: Relationship with the EPA/Arachidonic Acid Ratio

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