The cardiovascular protective role of docosahexaenoic acid

McLennan, Peter L; Howe, Peter R. C.; Abeywardena, Mahinda Y.; Müggli, Reto; Raederstorff, Daniel; Mano, Mark T.; Rayner, Tim; Head, Richard

doi:10.1016/0014-2999(95)00861-6

Cited by 177 publications

(147 citation statements)

References 29 publications

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“…9 -14,18 -20,30 -32 Although fish oils often contain mainly EPA, the myocardium, including mitochondrial membrane, accumulates DHA as the principal n-3 PUFA, even after feeding purified EPA. 13 We previously reported the effects of the very diets used in the present study, 10 demonstrating high incorporation of DHA with fish oil feeding. Membrane fatty acid modulation may modify a wide variety of intracellular and membrane events, such as ion flux, respiratory electron transport, carrier-mediated transport, membrane-bound enzyme activity, receptor function, intracellular lipid-based second messengers, and eicosanoid synthesis.…”

Section: Effects Of Dietary Lipids Onmentioning

confidence: 49%

Cardiac Membrane Fatty Acid Composition Modulates Myocardial Oxygen Consumption and Postischemic Recovery of Contractile Function

2002

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Background-Regular fish consumption is associated with low cardiovascular disease morbidity and mortality. Fish oils modify cardiac membrane phospholipid fatty acid composition with potent antiarrhythmic effects. We tested the effects of dietary fish oil on ventricular hemodynamics and myocardial oxygen consumption (MVO 2 ). Methods and Results-Male Wistar rats were fed for 16 weeks on a reference diet rich in n-6 polyunsaturated fatty acids (PUFA), a diet rich in saturated animal fat (SAT), or a diet rich in n-3 PUFA from fish oil. Isolated working hearts were perfused with porcine erythrocytes (40% hematocrit) at 75 mm Hg afterload with variable preload (5 to 20 mm Hg) or with low coronary flow ischemia with maintained afterload, preload, and heart rate, then reperfused. MVO 2 was low and coronary perfusion reserve high in n-3 PUFA hearts, and cardiac output increased with workload. The n-3 PUFA reduced ischemic markers-acidosis, K ϩ , lactate, and creatine kinase-and increased contractile recovery during reperfusion. SAT hearts had high MVO 2 , low coronary perfusion reserve, and poor contractile function and recovery. Dietary differences in MVO 2 were abolished by KCl arrest (basal metabolism) or ruthenium red (3.4 mol/L) but not by ryanodine (1 nmol/L). Fish oil or ryanodine, but not ruthenium red, prevented ventricular fibrillation in reperfusion. Conclusions-Dietary fish oil directly influenced heart function and improved cardiac responses to ischemia and reperfusion. The n-3 PUFA reduced oxygen consumption at any given work output and increased postischemic recovery. Thus, direct effects on myocardial function may contribute to the altered cardiovascular disease profile associated with fish consumption.

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Section: Effects Of Dietary Lipids Onmentioning

confidence: 49%

Cardiac Membrane Fatty Acid Composition Modulates Myocardial Oxygen Consumption and Postischemic Recovery of Contractile Function

2002

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“…Media were removed from semiconfluent monolayers (ϳ75%) and replaced with Hanks' buffer (37°C, 10 ml) containing HEPES, 10 mM, pH 7.4, and [1-14 C]DHA (55 mCi/mmol, American Radiolabeled Chemicals, Inc., 10 M), or unlabeled C22:6 (ϳ10 M, Oxford Biomedical Research) was added in EtOH (5-10 l). Cells were placed in an incubator with an atmosphere of 5% CO 2 at 37°C for 90 min, and aliquots (100 l) were removed at 30-min intervals and analyzed by scintillation counting to determine cellular [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]DHA. At 90 min, buffer was removed and cells were washed with Hanks' buffer (10 ml, 37°C).…”

Section: Methodsmentioning

confidence: 99%

Novel Docosatrienes and 17S-Resolvins Generated from Docosahexaenoic Acid in Murine Brain, Human Blood, and Glial Cells

Hong

Gronert

Devchand

et al. 2003

Journal of Biological Chemistry

925

1,051

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Docosahexaenoic acid (DHA, C22:6) is highly enriched in brain, synapses, and retina and is a major -3 fatty acid. Deficiencies in this essential fatty acid are reportedly associated with neuronal function, cancer, and inflammation. Here, using new lipidomic analyses employing high performance liquid chromatography coupled with a photodiode-array detector and a tandem mass spectrometer, a novel series of endogenous mediators was identified in blood, leukocytes, brain, and glial cells as 17S-hydroxy-containing docosanoids denoted as docosatrienes (the main bioactive member of the series was 10,17S-docosatriene) and 17S series resolvins. These novel mediators were biosynthesized via epoxide-containing intermediates and proved potent (pico-to nanomolar range) regulators of both leukocytes reducing infiltration in vivo and glial cells blocking their cytokine production. These results indicate that DHA is the precursor to potent protective mediators generated via enzymatic oxygenations to novel docosatrienes and 17S series resolvins that each regulate events of interest in inflammation and resolution.

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“…Primarily via the diet, DHA has been reported to have positive effects on an enormous variety of human afflictions including cancer [2,3], heart disease [4], rheumatoid arthritis [5], asthma [6], lupus [7], alcoholism [8], visual acuity [9], kidney disease [10], respiratory disease [11], peroxisomal disorders (Zellweger's Syndrome) [12], dermatitis [13], psoriasis [14], cystic fibrosis [15], Crohn's Disease [16], schizophrenia [17], depression [18], aggression [19l and brain development [20], malaria [21], multiple sclerosis [22], migraine headaches [23] and even suicide [18]. In fact, it is hard to find any human disorder that has not been tested with DHA.…”

Section: Dha: Health Effectsmentioning

confidence: 99%

Docosahexaenoic acid affects cell signaling by altering lipid rafts

et al. 2005

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-With 22 carbons and 6 double bonds docosahexaenoic acid (DHA) is the longest and most unsaturated fatty acid commonly found in membranes. It represents the extreme example of a class of important human health promoting agents known as omega-3 fatty acids. DHA is particularly abundant in retinal and brain tissue, often comprising about 50% of the membrane's total acyl chains. Inadequate amounts of DHA have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities to depression and suicide. The molecular mode of action of DHA, while not yet understood, has been the focus of our research. Here we briefly summarize how DHA affects membrane physical properties with an emphasis on membrane signaling domains known as rafts. We report the uptake of DHA into brain phosphatidylethanolamines and the subsequent exclusion of cholesterol from the DHA-rich membranes. We also demonstrate that DHA-induced apoptosis in MDA-MB-231 breast cancer cells is associated with externalization of phosphatidylserine and membrane disruption ("blebbing"). We conclude with a proposal of how DHA incorporation into membranes may control cell biochemistry and physiology. apoptosis / docosahexaenoic acid / lipid rafts / membranes / phospholipids

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The cardiovascular protective role of docosahexaenoic acid

Cited by 177 publications

References 29 publications

Cardiac Membrane Fatty Acid Composition Modulates Myocardial Oxygen Consumption and Postischemic Recovery of Contractile Function

Cardiac Membrane Fatty Acid Composition Modulates Myocardial Oxygen Consumption and Postischemic Recovery of Contractile Function

Novel Docosatrienes and 17S-Resolvins Generated from Docosahexaenoic Acid in Murine Brain, Human Blood, and Glial Cells

Docosahexaenoic acid affects cell signaling by altering lipid rafts

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