Eicosapentaenoic Acid Suppresses Basal and Insulin-Stimulated Endothelin-1 Production in Human Endothelial Cells

Chisaki, Keigo; Okuda, Yukichi; Suzuki, Seiji; Miyauchi, Takashi; Soma, Masaaki; Ohkoshi, Norio; Sone, Hirohito; Yamada, Nobuhiro; Nakajima, Toshiaki

doi:10.1291/hypres.26.655

Cited by 27 publications

(15 citation statements)

References 44 publications

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“…The molecular mechanisms underlying these associations are, however, far from clear. Whereas monoand polyunsaturated FFAs, such as oleate (C18:1 9), linoleate (C18:2 6), arachidonate (C20:4 6), eicosapentaenoate (C20:5 3), and docosahexaenoate (C22:6 3), have been convincingly demonstrated to modulate endothelial functions (23)(24)(25)(26)(27)(28), very little is known about the role of saturated FFAs in vascular complications.…”

Section: Discussionmentioning

confidence: 99%

Palmitate-Induced Interleukin-6 Expression in Human Coronary Artery Endothelial Cells

Staiger

Staiger²,

Stefan³

et al. 2004

Diabetes

146

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Obesity-linked insulin resistance is associated with chronic inflammation and cardiovascular complications. Free fatty acids (FFAs) are prominent candidates for the molecular link between these disorders. In this study, we determined whether FFAs contribute to vascular inflammation via induction of interleukin (IL)-6 in coronary artery endothelial cells (CAECs) and coronary artery smooth muscle cells (CASMCs) and whether this is reflected in vivo. In contrast to our findings regarding IL-6 and gp130 (the glycoprotein of 130 kDa) expression, IL-6 receptor mRNA expression was very low in these cells. Palmitate, but not linoleate, induced a significant increase in IL-6 mRNA expression in CAECs (P < 0.001) and, to a less relevant extent, in CASMCs (P < 0.01). gp130 remained unaffected. As to potency, palmitate was comparable with the IL-6؊inducer IL-1␤. To substantiate our in vitro data, we examined the plasma FFA pattern in 54 healthy human subjects and studied the relation of individual FFAs with plasma IL-6. IL-6 levels correlated with palmitate, but not with other abundant FFAs, even after adjusting for body fat (r ‫؍‬ 0.33, P < 0.05) and total FFAs (r ‫؍‬ 0.29, P < 0.05). We show here that the common plasma FFA palmitate induces high levels of IL-6 in CAECs. Furthermore, palmitate correlates with IL-6 in vivo. This points to a potential contribution of palmitate to vascular inflammation. Diabetes 53: 3209 -3216, 2004

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Section: Discussionmentioning

confidence: 99%

Palmitate-Induced Interleukin-6 Expression in Human Coronary Artery Endothelial Cells

Staiger

Staiger²,

Stefan³

et al. 2004

Diabetes

146

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“…Inasmuch as 3-300 M EPA has been shown to upregulate nitric oxide production in endothelial cells (10,34), we used 1-100 M EPA to generate a response curve in the present study. In our preliminary experiments, we used 1-100 M (specifically, 1, 3, 10, and 30 M) EPA to conduct an EPA dose-response study.…”

Section: Cardiomyocyte Response To Varying Doses Of Epa After 10 ϫ10 mentioning

confidence: 99%

Eicosapentaenoic acid prevents endothelin-1-induced cardiomyocyte hypertrophy in vitro through the suppression of TGF-β1 and phosphorylated JNK

Shimojo¹,

Jesmin²,

Zaedi³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The cardiovascular benefit of fish oil in humans and experimental animals has been reported. Endothelin (ET)-1 is a well-known cardiac hypertrophic factor. However, although many studies link a fish oil extract, eicosapentaenoic acid (EPA), to cardiac protection, the effects of EPA on cardiac hypertrophy and underlying mechanism(s) are unclear. The present study investigated whether EPA prevents ET-1-induced cardiomyocyte hypertrophy; the potential pathways likely to underlie such an effect were also investigated. Cardiomyocytes were isolated from neonatal rat heart, cultured for 3 days, and then treated for 24 h with vehicle only (control), treated with 0.1 nM ET-1 only, or pretreated with 10 microM EPA and then treated with 0.1 nM ET-1. The cells were harvested, and changes in cell surface area, protein synthesis, expression of a cytoskeletal (alpha-actinin) protein, and cell signaling were analyzed. ET-1 induced a 97% increase in cardiomyocyte surface area, a 72% increase in protein synthesis rate, and an increase in expression of alpha-actinin and signaling molecule [transforming growth factor-beta 1 (TGF-beta 1), c-Jun NH2-terminal kinase (JNK), and c-Jun]. Development of these ET-1-induced cellular changes was attenuated by EPA. Moreover, the hypertrophied cardiomyocytes showed a 1.5- and a 1.7-fold increase in mRNA expression of atrial and brain natriuretic peptides, the classical molecular markers of cardiac hypertrophy, respectively; these changes were also suppressed by EPA. Here we show that ET-1 induces cardiomyocyte hypertrophy and expression of hypertrophic markers, possibly mediated by JNK and TGF-beta 1 signaling pathways. These ET-1-induced effects were blocked by EPA, a major fish oil ingredient, suggesting that fish oil may have beneficial protective effects on cardiac hypertrophy.

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“…Treatment with EPA, however, increases EPA levels in both plasma and tissues in a dose-dependent manner, thereby increasing the EPA:AA ratio [16][17][18]. EPA treatment also results in a corresponding decrease in plasma levels of AA and may, therefore, help reverse the EPA:AA ratio from being pro-inflammatory/proaggregatory to anti-inflammatory/anti-aggregatory ( Figure 3) [17,[19][20][21][22][23][24]. This review will focus on the role of the EPA:AA ratio as a potential prognostic marker and treatment target in cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

The eicosapentaenoic acid:arachidonic acid ratio and its clinical utility in cardiovascular disease

Nelson

Raskin²

2019

Postgraduate Medicine

117

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Eicosapentaenoic acid (EPA) is a key anti-inflammatory/anti-aggregatory long-chain polyunsaturated omega-3 fatty acid. Conversely, the omega-6 fatty acid, arachidonic acid (AA) is a precursor to a number of pro-inflammatory/pro-aggregatory mediators. EPA acts competitively with AA for the key cyclooxygenase and lipoxygenase enzymes to form less inflammatory products. As a result, the EPA:AA ratio may be a marker of chronic inflammation, with a lower ratio corresponding to higher levels of inflammation. It is now well established that inflammation plays an important role in cardiovascular disease. This review examines the role of the EPA:AA ratio as a marker of cardiovascular disease and the relationship between changes in the ratio (mediated by EPA intake) and changes in cardiovascular risk. Epidemiological studies have shown that a lower EPA:AA ratio is associated with an increased risk of coronary artery disease, acute coronary syndrome, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and vascular disease. Increasing the EPA:AA ratio through treatment with purified EPA has been shown in clinical studies to be effective in primary and secondary prevention of coronary artery disease and reduces the risk of cardiovascular events following percutaneous coronary intervention. The EPA:AA ratio is a valuable predictor of cardiovascular risk. Results from ongoing clinical trials will help to define thresholds for EPA treatment associated with better clinical outcomes.

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Eicosapentaenoic Acid Suppresses Basal and Insulin-Stimulated Endothelin-1 Production in Human Endothelial Cells

Cited by 27 publications

References 44 publications

Palmitate-Induced Interleukin-6 Expression in Human Coronary Artery Endothelial Cells

Palmitate-Induced Interleukin-6 Expression in Human Coronary Artery Endothelial Cells

Eicosapentaenoic acid prevents endothelin-1-induced cardiomyocyte hypertrophy in vitro through the suppression of TGF-β1 and phosphorylated JNK

The eicosapentaenoic acid:arachidonic acid ratio and its clinical utility in cardiovascular disease

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