ArticlePloS one2014
Redox-sensitive induction of Src/PI3-kinase/Akt and MAPKs pathways activate eNOS in response to EPA:DHA 6:1.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 49 citations in OpenAlex.
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- Ischemic heart disease burden attributable to inadequate omega-3 fatty acid intake in Chinese adults, 1990-2021: an Age-Period-Cohort analysis of the Global Burden of Disease study.Frontiers in nutrition · 2025Article
- Harnessing nutrients and natural products for sustainable drug development against aging.Frontiers in pharmacology · 2025Review
- Antarctic Krill Oil fromInternational journal of molecular sciences · 2023Article
- The effects of dietary inclusion of Camelina sativa on performance and ascites incidence in broilers subjected to cold exposure.Veterinary medicine and science · 2023Article
- The Protective Effects of Eicosapentaenoic Acid for Stress-induced Accelerated Senescence in Vascular Endothelial Cells.International journal of medical sciences · 2023Article
- Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation.Oxidative medicine and cellular longevity · 2021Article
- A Mixture of Algae and Extra Virgin Olive Oils Attenuates the Cardiometabolic Alterations Associated with Aging in Male Wistar Rats.Antioxidants (Basel, Switzerland) · 2020Article
- Oral Intake of EPA:DHA 6:1 by Middle-Aged Rats for One Week Improves Age-Related Endothelial Dysfunction in Both the Femoral Artery and Vein: Role of Cyclooxygenases.International journal of molecular sciences · 2020Article
- EPA and DHA Inhibit Myogenesis and Downregulate the Expression of Muscle-related Genes in C2C12 Myoblasts.Genes · 2019Article
- Potential usefulness of methyl gallate in the treatment of experimental colitis.Inflammopharmacology · 2018Article
- Superoxide inhibition restores endothelium-dependent dilatation in aging arteries by enhancing impaired adherens junctions.American journal of physiology. Heart and circulatory physiology · 2018Article
- EPA:DHA 6:1 prevents angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase- and COX-derived oxidative stress.Hypertension research : official journal of the Japanese Society of Hypertension · 2017Article
- Senescence of Pancreas in Middle-Aged Rats with Normal Vascular Function.Annals of transplantation · 2017Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsOmega-3 fatty acid products containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have vasoprotective effects, in part, by stimulating the endothelial formation of nitric oxide (NO). This study determined the role of the EPA:DHA ratio and amount, and characterized the mechanism leading to endothelial NO synthase (eNOS) activation. METHODS AND
resultsEPA:DHA 6∶1 and 9∶1 caused significantly greater endothelium-dependent relaxations in porcine coronary artery rings than EPA:DHA 3∶1, 1∶1, 1∶3, 1∶6, 1∶9, EPA and DHA alone, and EPA:DHA 6∶1 with a reduced EPA + DHA amount, which were inhibited by an eNOS inhibitor. Relaxations to EPA:DHA 6∶1 were insensitive to cyclooxygenase inhibition, and reduced by inhibitors of either oxidative stress, Src kinase, PI3-kinase, p38 MAPK, MEK, or JNK. EPA:DHA 6∶1 induced phosphorylation of Src, Akt, p38 MAPK, ERK, JNK and eNOS; these effects were inhibited by MnTMPyP. EPA:DHA 6∶1 induced the endothelial formation of ROS in coronary artery sections as assessed by dihydroethidium, and of superoxide anions and hydrogen peroxide in cultured endothelial cells as assessed by electron spin resonance with the spin probe CMH, and the Amplex Red based assay, respectively.
conclusionOmega-3 fatty acids cause endothelium-dependent NO-mediated relaxations in coronary artery rings, which are dependent on the EPA:DHA ratio and amount, and involve an intracellular activation of the redox-sensitive PI3-kinase/Akt and MAPKs pathways to activate eNOS.
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