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Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 July 2017) | Viewed by 86588

Special Issue Editors

Cardiology Clinic, ‘Hippokration’ General Hospital, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece
Interests: clinical and molecular cardiology; endothelial function; arterial stiffness
Special Issues, Collections and Topics in MDPI journals
First Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical School, Vasilissis Sofias 114, TK 115 28 Athens, Greece

Special Issue Information

Dear Colleagues,

In the first part of the present supplement, we intent to elucidate the role of Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) in systemic low grade and vascular inflammation and their impact on adhesion molecules, cytokines, oxidative stress, ROS production, as well as on the thrombosis-fibrinolysis system. We will also present and discuss the effects of Omega-3 PUFAs on endothelial and vascular function, as indicated by endothelial dependent and independent dilatation, by pulse wave velocity, carotid intima media thickness and by aortic distensibility.

In the second part of the proposed supplement, we focus on the therapeutic potential of Omega-3 PUFAs in patients with hypertension, stable angina pectoris, heart failure, acute coronary syndromes atrial fibrillation and hyperlipidemia.

Potential topics may include:

1) The physiology of Omega-3 polyunsaturated fatty acids

2) Omega-3 polyunsaturated fatty acids and cardiovascular prognosis

3) The role of Omega-3 polyunsaturated fatty acids on vascular inflammation

4) Omega-3 polyunsaturated fatty acids and oxidative stress

5) The role of Omega-3 polyunsaturated fatty acids on thrombosis fibrinolysis system

6) The role of Omega-3 polyunsaturated fatty acids on endothelial function

7) The role of Omega-3 polyunsaturated fatty acids on vascular function

8) Omega-3 polyunsaturated fatty acids in the treatment of atrial arterial hypertension

9) Omega-3 polyunsaturated fatty acids in the treatment of stable angina pectoris

10) Omega-3 polyunsaturated fatty acids in the treatment of heart failure

11) Omega-3 polyunsaturated fatty acids in the treatment of Acute Coronary syndromes

12) Omega-3 polyunsaturated fatty acids in the treatment of metabolic syndrome and hyperlipidemia

13) Omega-3 polyunsaturated fatty acids in the treatment of atrial fibrillation

Prof. Dimitris Tousoulis
Dr. Evangelos Oikonomou
Guest Editors

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Published Papers (14 papers)

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Research

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898 KiB  
Article
Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial
by Martin H. De Borst, Leandro C. Baia, Ellen K. Hoogeveen, Erik J. Giltay, Gerjan Navis, Stephan J. L. Bakker, Johanna M. Geleijnse, Daan Kromhout and Sabita S. Soedamah-Muthu
Nutrients 2017, 9(11), 1233; https://doi.org/10.3390/nu9111233 - 11 Nov 2017
Cited by 7 | Viewed by 4641
Abstract
Fibroblast growth factor 23 (FGF23) is an independent risk factor for cardiovascular mortality in chronic kidney disease. Omega-3 (n-3) fatty acid consumption has been inversely associated with FGF23 levels and with cardiovascular risk. We examined the effect of marine n-3 fatty acids eicosapentaenoic [...] Read more.
Fibroblast growth factor 23 (FGF23) is an independent risk factor for cardiovascular mortality in chronic kidney disease. Omega-3 (n-3) fatty acid consumption has been inversely associated with FGF23 levels and with cardiovascular risk. We examined the effect of marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and plant-derived alpha-linolenic acid (ALA) on plasma FGF23 levels in post-myocardial infarction patients with chronic kidney disease. In the randomized double-blind Alpha Omega Trial, 4837 patients with a history of myocardial infarction aged 60–80 years (81% men) were randomized to one of four trial margarines supplemented with a targeted additional intake of 400 mg/day EPA and DHA, 2 g/day ALA, EPA-DHA plus ALA, or placebo for 41 months. In a subcohort of 336 patients with an eGFR < 60 mL/min/1.73 m2 (creatinine-cystatin C-based CKD-EPI formula), plasma C-terminal FGF23 was measured by ELISA at baseline and end of follow-up. We used analysis of covariance to examine treatment effects on FGF23 levels adjusted for baseline FGF23. Patients consumed 19.8 g margarine/day on average, providing an additional amount of 236 mg/day EPA with 158 mg/day DHA, 1.99 g/day ALA or both, in the active intervention groups. Over 79% of patients were treated with antihypertensive and antithrombotic medication and statins. At baseline, plasma FGF23 was 150 (128 to 172) RU/mL (mean (95% CI)). After 41 months, overall FGF23 levels had increased significantly (p < 0.0001) to 212 (183 to 241) RU/mL. Relative to the placebo, the treatment effect of EPA-DHA was indifferent, with a mean change in FGF23 (95% CI) of −17 (−97, 62) RU/mL (p = 0.7). Results were similar for ALA (36 (−42, 115) RU/mL) and combined EPA-DHA and ALA (34 (−44, 113) RU/mL). Multivariable adjustment, pooled analyses, and subgroup analyses yielded similar non-significant results. Long-term supplementation with modest quantities of EPA-DHA or ALA does not reduce plasma FGF23 levels when added to cardiovascular medication in post-myocardial patients with chronic kidney disease. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Article
Red Blood Cell Eicosapentaenoic Acid Inversely Relates to MRI-Assessed Carotid Plaque Lipid Core Burden in Elders at High Cardiovascular Risk
by Núria Bargalló, Rosa Gilabert, Edwin-Saúl Romero-Mamani, Montserrat Cofán, Philip C. Calder, Montserrat Fitó, Dolores Corella, Jordi Salas-Salvadó, Miguel Ruiz-Canela, Ramon Estruch, Emilio Ros and Aleix Sala-Vila
Nutrients 2017, 9(9), 1036; https://doi.org/10.3390/nu9091036 - 20 Sep 2017
Cited by 4 | Viewed by 5868
Abstract
Supplemental marine omega-3 eicosapentaenoic acid (EPA) has an anti-atherosclerotic effect. Clinical research on EPA supplied by the regular diet and atherosclerosis is scarce. In the framework of the PREvención con DIeta MEDiterránea (PREDIMED) trial, we conducted a cross-sectional study in 161 older individuals [...] Read more.
Supplemental marine omega-3 eicosapentaenoic acid (EPA) has an anti-atherosclerotic effect. Clinical research on EPA supplied by the regular diet and atherosclerosis is scarce. In the framework of the PREvención con DIeta MEDiterránea (PREDIMED) trial, we conducted a cross-sectional study in 161 older individuals at high vascular risk grouped into different stages of carotid atherosclerosis severity, including those without ultrasound-detected atheroma plaque (n = 38), with plaques <2.0 mm thick (n = 65), and with plaques ≥2.0 mm (n = 79). The latter were asked to undergo contrast-enhanced 3T magnetic resonance imaging (MRI) and were subsequently grouped into absence (n = 31) or presence (n = 27) of MRI-detectable plaque lipid, a main feature of unstable atheroma plaques. We determined the red blood cell (RBC) proportion of EPA (a valid marker of long-term EPA intake) at enrolment by gas chromatography. In multivariate models, EPA related inversely to MRI-assessed plaque lipid volume, but not to maximum intima-media thickness of internal carotid artery, plaque burden, or MRI-assessed normalized wall index. The inverse association between EPA and plaque lipid content in patients with advanced atherosclerosis supports the notion that this fatty acid might improve cardiovascular health through stabilization of advanced atheroma plaques. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Article
Low Docosahexaenoic Acid, Dihomo-Gamma-Linolenic Acid, and Arachidonic Acid Levels Associated with Long-Term Mortality in Patients with Acute Decompensated Heart Failure in Different Nutritional Statuses
by Shohei Ouchi, Tetsuro Miyazaki, Kazunori Shimada, Yurina Sugita, Megumi Shimizu, Azusa Murata, Takao Kato, Tatsuro Aikawa, Shoko Suda, Tomoyuki Shiozawa, Masaru Hiki, Shuhei Takahashi, Hiroshi Iwata, Takatoshi Kasai, Katsumi Miyauchi and Hiroyuki Daida
Nutrients 2017, 9(9), 956; https://doi.org/10.3390/nu9090956 - 30 Aug 2017
Cited by 14 | Viewed by 5335
Abstract
The clinical significance of polyunsaturated fatty acids (PUFAs) in acute decompensated heart failure (ADHF) in various nutritional statuses remains unclear. For this study, we enrolled 267 patients with ADHF admitted to the cardiac intensive care unit at Juntendo University hospital between April 2012 [...] Read more.
The clinical significance of polyunsaturated fatty acids (PUFAs) in acute decompensated heart failure (ADHF) in various nutritional statuses remains unclear. For this study, we enrolled 267 patients with ADHF admitted to the cardiac intensive care unit at Juntendo University hospital between April 2012 and March 2014. The association between long-term mortality, the geriatric nutritional risk index (GNRI), and levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) was investigated. The median age was 73 (64–82) years, and mortality was 29% (62 patients). The event-free survival rates for all-cause death were higher in patients with high PUFA levels or GNRI than in those with low PUFA levels or GNRI (p < 0.05 for all). In particular, high DGLA in the low-GNRI group and high DHA or AA in the high-GNRI group were associated with high event-free survival (p < 0.05 for all). After accounting for confounding variables, DHA, DGLA, and AA, but not EPA, were associated with long-term mortality (p < 0.01 for all). This study concludes that in patients with ADHF, decreased levels of DHA, DGLA, and AA are independently associated with long-term mortality in the various nutritional statuses. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Article
Dietary Fish and Long-Chain n-3 Polyunsaturated Fatty Acids Intake and Risk of Atrial Fibrillation: A Meta-Analysis
by Fu-Rong Li, Guo-Chong Chen, Jiabi Qin and Xianbo Wu
Nutrients 2017, 9(9), 955; https://doi.org/10.3390/nu9090955 - 29 Aug 2017
Cited by 14 | Viewed by 4902
Abstract
Findings on the association between long-term intake of fish or long-chain n-3 polyunsaturated fatty acids (PUFAs) and risk of atrial fibrillation (AF) are inconsistent in observational studies. We conducted a meta-analysis of prospective studies to separately examine the associations between fish consumption [...] Read more.
Findings on the association between long-term intake of fish or long-chain n-3 polyunsaturated fatty acids (PUFAs) and risk of atrial fibrillation (AF) are inconsistent in observational studies. We conducted a meta-analysis of prospective studies to separately examine the associations between fish consumption and dietary intake of n-3 PUFAs with the risk of AF. A systematic search was conducted in PubMed and Embase to identify relevant studies. Risk estimates were combined using a random-effect model. Seven prospective cohort studies covering 206,811 participants and 12,913 AF cases were eligible. The summary relative risk of AF for the highest vs. lowest category of fish consumption and dietary intake of n-3 PUFAs was 1.01(95% confidence interval: 0.94–1.09) and 1.03 (95% confidence interval: 0.97–1.09), respectively. These null associations persisted in subgroup and dose-response analyses. There was little evidence of publication bias. This meta-analysis suggests that neither long-term intake of fish, nor of n-3 PUFAs were significantly associated with lower risk of AF. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Article
Genome-Wide Interaction Study of Omega-3 PUFAs and Other Fatty Acids on Inflammatory Biomarkers of Cardiovascular Health in the Framingham Heart Study
by Jenna Veenstra, Anya Kalsbeek, Jason Westra, Craig Disselkoen, Caren E. Smith and Nathan Tintle
Nutrients 2017, 9(8), 900; https://doi.org/10.3390/nu9080900 - 18 Aug 2017
Cited by 6 | Viewed by 4870
Abstract
Numerous genetic loci have been identified as being associated with circulating fatty acid (FA) levels and/or inflammatory biomarkers of cardiovascular health (e.g., C-reactive protein). Recently, using red blood cell (RBC) FA data from the Framingham Offspring Study, we conducted a genome-wide association study [...] Read more.
Numerous genetic loci have been identified as being associated with circulating fatty acid (FA) levels and/or inflammatory biomarkers of cardiovascular health (e.g., C-reactive protein). Recently, using red blood cell (RBC) FA data from the Framingham Offspring Study, we conducted a genome-wide association study of over 2.5 million single nucleotide polymorphisms (SNPs) and 22 RBC FAs (and associated ratios), including the four Omega-3 FAs (ALA, DHA, DPA, and EPA). Our analyses identified numerous causal loci. In this manuscript, we investigate the extent to which polyunsaturated fatty acid (PUFA) levels moderate the relationship of genetics to cardiovascular health biomarkers using a genome-wide interaction study approach. In particular, we test for possible gene–FA interactions on 9 inflammatory biomarkers, with 2.5 million SNPs and 12 FAs, including all Omega-3 PUFAs. We identified eighteen novel loci, including loci which demonstrate strong evidence of modifying the impact of heritable genetics on biomarker levels, and subsequently cardiovascular health. The identified genes provide increased clarity on the biological functioning and role of Omega-3 PUFAs, as well as other common fatty acids, in cardiovascular health, and suggest numerous candidate loci for future replication and biological characterization. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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2562 KiB  
Article
Omega 3 Polyunsaturated Fatty Acids Improve Endothelial Dysfunction in Chronic Renal Failure: Role of eNOS Activation and of Oxidative Stress
by Michela Zanetti, Gianluca Gortan Cappellari, Davide Barbetta, Annamaria Semolic and Rocco Barazzoni
Nutrients 2017, 9(8), 895; https://doi.org/10.3390/nu9080895 - 18 Aug 2017
Cited by 32 | Viewed by 5621
Abstract
Background: Endothelial dysfunction is a key vascular alteration in chronic kidney disease (CKD). Omega 3 (n-3) polyunsaturated fatty acids (PUFA) reduce vascular oxidative stress and inflammation. We investigated whether n-3 PUFA could reverse endothelial dysfunction in CKD by improving endothelial [...] Read more.
Background: Endothelial dysfunction is a key vascular alteration in chronic kidney disease (CKD). Omega 3 (n-3) polyunsaturated fatty acids (PUFA) reduce vascular oxidative stress and inflammation. We investigated whether n-3 PUFA could reverse endothelial dysfunction in CKD by improving endothelial nitric oxide synthase (eNOS) function and oxidative stress. Methods: 5/6 nephrectomized male Wistar rats (CKD; n = 10) and sham operated animals (SHAM; n = 10) were treated for 6 weeks with standard diet. An additional group of CKD rats were fed an n-3 PUFA enriched diet (CKD + PUFA; n = 10). We then measured endothelium-dependent (EDD) and -independent vasodilation, markers of endothelial function and of oxidative stress in thoracic aortas. Results: Compared to SHAM, in CKD aortas EDD and eNOS expression were reduced (p < 0.05) and 3-nitrotyrosine levels were increased, while expression of NADPH oxidase subunits NOX4 and p22phox was similar. In-vitro incubation with Tiron failed to reverse endothelial dysfunction in CKD. In CKD + PUFA, EDD improved (p < 0.05) compared with CKD rats, while blockade of eNOS by L-NAME worsened EDD. These effects were accompanied by increased (p < 0.05) eNOS and reduced (p < 0.05) expression of NOX4 and 3-nitrotyrosine levels. Conclusion: Collectively, these findings indicate that n-3 PUFA improve endothelial dysfunction by restoring NO bioavailability in CKD. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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3349 KiB  
Article
Suppression of Wnt Signaling and Osteogenic Changes in Vascular Smooth Muscle Cells by Eicosapentaenoic Acid
by Yukihiro Saito, Kazufumi Nakamura, Daiji Miura, Kei Yunoki, Toru Miyoshi, Masashi Yoshida, Norifumi Kawakita, Tomonari Kimura, Megumi Kondo, Toshihiro Sarashina, Satoshi Akagi, Atsuyuki Watanabe, Nobuhiro Nishii, Hiroshi Morita and Hiroshi Ito
Nutrients 2017, 9(8), 858; https://doi.org/10.3390/nu9080858 - 10 Aug 2017
Cited by 18 | Viewed by 5507
Abstract
Vascular medial calcification is often observed in patients with arteriosclerosis. It is also associated with systolic hypertension, wide pulse pressure, and fluctuation of blood pressure, which results in cardiovascular events. Eicosapentaenoic acid (EPA) has been shown to suppress vascular calcification in previous animal [...] Read more.
Vascular medial calcification is often observed in patients with arteriosclerosis. It is also associated with systolic hypertension, wide pulse pressure, and fluctuation of blood pressure, which results in cardiovascular events. Eicosapentaenoic acid (EPA) has been shown to suppress vascular calcification in previous animal experiments. We investigated the inhibitory effects of EPA on Wnt signaling, which is one of the important signaling pathways involved in vascular calcification. Intake of food containing 5% EPA resulted in upregulation of the mRNA expression of Klotho, an intrinsic inhibitor of Wnt signaling, in the kidneys of wild-type mice. Expression levels of β-catenin, an intracellular signal transducer in the Wnt signaling pathway, were increased in the aortas of Klotho mutant (kl/kl) mice compared to the levels in the aortas of wild-type mice. Wnt3a or BIO, a GSK-3 inhibitor that activates β-catenin signaling, upregulated mRNA levels of AXIN2 and LEF1, Wnt signaling marker genes, and RUNX2 and BMP4, early osteogenic genes, in human aorta smooth muscle cells. EPA suppressed the upregulation of AXIN2 and BMP4. The effect of EPA was cancelled by T0070907, a PPARγ inhibitor. The results suggested that EPA could suppress vascular calcification via the inhibition of Wnt signaling in osteogenic vascular smooth muscle cells via PPARγ activation. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Article
Impact of Biological Feedback and Incentives on Blood Fatty Acid Concentrations, Including Omega-3 Index, in an Employer-Based Wellness Program
by Michael I. McBurney and Julia K. Bird
Nutrients 2017, 9(8), 842; https://doi.org/10.3390/nu9080842 - 05 Aug 2017
Cited by 2 | Viewed by 4928
Abstract
Eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) are important fatty acids for the retina and brain. More than 95% of Americans have suboptimal EPA + DHA blood concentrations. This cross-sectional employer-based study assessed whole blood fatty acid levels of volunteers participating [...] Read more.
Eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) are important fatty acids for the retina and brain. More than 95% of Americans have suboptimal EPA + DHA blood concentrations. This cross-sectional employer-based study assessed whole blood fatty acid levels of volunteers participating in an onsite wellness biometric screening program and was designed to determine if an incentive, a $5 coupon for a 90-day supply of fish oil supplement typically costing $18–30, stimulated incremental dietary behavior change relative to nutritional status assessment alone to increase EPA + DHA concentrations. Volunteers completed a dietary survey and finger stick blood samples were collected to be analyzed for fatty acid composition. In addition, 636 individuals participated in the initial onsite biometric screening. Three months later, and without prior knowledge, all employees were invited to a second screening. At the second screening, 198 employees volunteered for the first time and 149 employees had a second test (17.9%). At baseline, the average age (n = 834) was 45 year and omega-3 index was 5.0% with 41% female. EPA + DHA concentration, i.e., omega-3 index, was significantly lower in men (4.8%) than women (5.2%), as were DHA and linoleic acid (LA) concentrations (p < 0.05). Baseline omega-3 index was positively and linearly associated with omega-3 intake. Only 4% of volunteers had an omega-3 index >8% on initial screening. Among the 149 individuals with two measurements, omega-3 intake from supplements, but not food, increased significantly from 258 to 445 mg/d (p < 0.01) at the second test as did the omega-3 index (+0.21, p < 0.02). In this employed population, only 1% redeemed a coupon for an omega-3 supplement. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Article
Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs
by Dyuti Sharma, Estelle Aubry, Thavarak Ouk, Ali Houeijeh, Véronique Houfflin-Debarge, Rémi Besson, Philippe Deruelle and Laurent Storme
Nutrients 2017, 9(7), 761; https://doi.org/10.3390/nu9070761 - 16 Jul 2017
Cited by 9 | Viewed by 4096
Abstract
Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep [...] Read more.
Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E− (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E− (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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2751 KiB  
Article
N-3 Polyunsaturated Fatty Acids Decrease the Protein Expression of Soluble Epoxide Hydrolase via Oxidative Stress-Induced P38 Kinase in Rat Endothelial Cells
by Takashi Okada, Katsutaro Morino, Fumiyuki Nakagawa, Masashi Tawa, Keiko Kondo, Osamu Sekine, Takeshi Imamura, Tomio Okamura, Satoshi Ugi and Hiroshi Maegawa
Nutrients 2017, 9(7), 654; https://doi.org/10.3390/nu9070654 - 24 Jun 2017
Cited by 10 | Viewed by 5748
Abstract
N-3 polyunsaturated fatty acids (PUFAs) improve endothelial function. The arachidonic acid-derived metabolites (epoxyeicosatrienoic acids (EETs)) are part of the endothelial hyperpolarization factor and are vasodilators independent of nitric oxide. However, little is known regarding the regulation of EET concentration by docosahexaenoic acid [...] Read more.
N-3 polyunsaturated fatty acids (PUFAs) improve endothelial function. The arachidonic acid-derived metabolites (epoxyeicosatrienoic acids (EETs)) are part of the endothelial hyperpolarization factor and are vasodilators independent of nitric oxide. However, little is known regarding the regulation of EET concentration by docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in blood vessels. Sprague-Dawley rats were fed either a control or fish oil diet for 3 weeks. Compared with the control, the fish oil diet improved acetylcholine-induced vasodilation and reduced the protein expression of soluble epoxide hydrolase (sEH), a key EET metabolic enzyme, in aortic strips. Both DHA and EPA suppressed sEH protein expression in rat aorta endothelial cells (RAECs). Furthermore, the concentration of 4-hydroxy hexenal (4-HHE), a lipid peroxidation product of n-3 PUFAs, increased in n-3 PUFA-treated RAECs. In addition, 4-HHE treatment suppressed sEH expression in RAECs, suggesting that 4-HHE (derived from n-3 PUFAs) is involved in this phenomenon. The suppression of sEH was attenuated by the p38 kinase inhibitor (SB203580) and by treatment with the antioxidant N-acetyl-L-cysteine. In conclusion, sEH expression decreased after n-3 PUFAs treatment, potentially through oxidative stress and p38 kinase. Mild oxidative stress induced by n-3 PUFAs may contribute to their cardio-protective effect. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Review

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296 KiB  
Review
Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs
by Narcis Tribulova, Barbara Szeiffova Bacova, Tamara Egan Benova, Vladimir Knezl, Miroslav Barancik and Jan Slezak
Nutrients 2017, 9(11), 1191; https://doi.org/10.3390/nu9111191 - 30 Oct 2017
Cited by 40 | Viewed by 7067
Abstract
Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated [...] Read more.
Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
1357 KiB  
Review
The Role of Omega-3 Fatty Acids in Reverse Cholesterol Transport: A Review
by Alex Pizzini, Lukas Lunger, Egon Demetz, Richard Hilbe, Guenter Weiss, Christoph Ebenbichler and Ivan Tancevski
Nutrients 2017, 9(10), 1099; https://doi.org/10.3390/nu9101099 - 06 Oct 2017
Cited by 81 | Viewed by 14031
Abstract
The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on cardiovascular disease have been studied extensively. However, it remains unclear to what extent n-3 PUFAs may impact Reverse Cholesterol Transport (RCT). RCT describes a mechanism by which excess cholesterol from peripheral tissues [...] Read more.
The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on cardiovascular disease have been studied extensively. However, it remains unclear to what extent n-3 PUFAs may impact Reverse Cholesterol Transport (RCT). RCT describes a mechanism by which excess cholesterol from peripheral tissues is transported to the liver for hepatobiliary excretion, thereby inhibiting foam cell formation and the development of atherosclerosis. The aim of this review is to summarize the literature and to provide an updated overview of the effects of n-3 PUFAs on key players in RCT, including apoliprotein AI (apoA-I), ATP-binding cassette transporter A1 (ABCA1), ABCG1, apoE, scavenger receptor class B type I (SR-BI), cholesteryl ester transfer protein (CETP), low-density lipoprotein receptor (LDLr), cholesterol 7 alpha-hydroxylase (CYP7A1) and ABCG5/G8. Based on current knowledge, we conclude that n-3 PUFAs may beneficially affect RCT, mainly by influencing high-density lipoprotein (HDL) remodeling and by promoting hepatobiliary sterol excretion. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Review
n-3 Polyunsaturated Fatty Acids and Metabolic Syndrome Risk: A Meta-Analysis
by Xiao-fei Guo, Xin Li, Meiqi Shi and Duo Li
Nutrients 2017, 9(7), 703; https://doi.org/10.3390/nu9070703 - 06 Jul 2017
Cited by 65 | Viewed by 6828
Abstract
The associations between n-3 polyunsaturated fatty acids (PUFAs) and metabolic syndrome (MetS) risk have demonstrated inconsistent results. The present study aimed to investigate whether higher circulating n-3 PUFAs and dietary n-3 PUFAs intake have a protective effect on MetS risk. [...] Read more.
The associations between n-3 polyunsaturated fatty acids (PUFAs) and metabolic syndrome (MetS) risk have demonstrated inconsistent results. The present study aimed to investigate whether higher circulating n-3 PUFAs and dietary n-3 PUFAs intake have a protective effect on MetS risk. A systematic literature search in the PubMed, Scopus, and Chinese National Knowledge Infrastructure (CNKI) databases was conducted up to March 2017. Odd ratios (ORs) from case-control and cross-sectional studies were combined using a random-effects model for the highest versus lowest category. The differences of n-3 PUFAs between healthy subjects and patients with MetS were calculated as weighted mean difference (WMD) by using a random-effects model. Seven case-control and 20 cross-sectional studies were included. A higher plasma/serum n-3 PUFAs was associated with a lower MetS risk (Pooled OR = 0.63, 95% CI: 0.49, 0.81). The plasma/serum n-3 PUFAs in controls was significantly higher than cases (WMD: 0.24; 95% CI: 0.04, 0.43), especially docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). However, no significant association was found between dietary intake of n-3 PUFAs or fish and MetS risk. The present study provides substantial evidence of a higher circulating n-3 PUFAs associated with a lower MetS risk. The circulating n-3 PUFAs can be regarded as biomarkers indicating MetS risk, especially DPA and DHA. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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Review
Effects of Long-Chain Omega-3 Polyunsaturated Fatty Acids on Endothelial Vasodilator Function and Cognition—Are They Interrelated?
by Julia C. Kuszewski, Rachel H. X. Wong and Peter R. C. Howe
Nutrients 2017, 9(5), 487; https://doi.org/10.3390/nu9050487 - 12 May 2017
Cited by 25 | Viewed by 6089
Abstract
Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) may improve brain functions by acting on endothelial cells in the cerebrovasculature to facilitate vasodilatation and perfusion. The aim of this review is to explore this hypothesis by analyzing the effect of LCn-3 PUFA supplementation on [...] Read more.
Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) may improve brain functions by acting on endothelial cells in the cerebrovasculature to facilitate vasodilatation and perfusion. The aim of this review is to explore this hypothesis by analyzing the effect of LCn-3 PUFA supplementation on systemic vasodilator and cognitive function and finding evidence to link LCn-3 PUFA intake, vasodilator function and cognition. Forty randomized controlled trials examining the effect of LCn-3 PUFA supplementation in humans on either endothelial vasodilator function or cognition were identified and pooled effects measured with a weighted analysis. Compared to placebo, LCn-3 PUFA tended to increase flow-mediated dilatation and significantly improved cognitive function. Emerging evidence links vasodilator dysfunction to cognitive impairment, but evidence that LCn-3 PUFA can improve cognition through enhancements of vasodilator function is still lacking. Further research is needed to determine: (1) whether LCn-3 PUFA can enhance dilatation of cerebral vessels; (2) if improvements in cerebrovascular responsiveness by LCn-3 PUFA are accompanied by cognitive benefits; and (3) the target population groups. Full article
(This article belongs to the Special Issue Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health)
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