Cardiovascular effects of marine omega-3 fatty acids

Saravanan, Palaniappan; Davidson, Neil C.; Schmidt, Erik Berg; Calder, Philip C.

doi:10.1016/s0140-6736(10)60445-x

Cited by 462 publications

(362 citation statements)

References 99 publications

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“…Injection of DHA into wild-type mice but not in Slo1 knockout mice significantly lowers blood pressure, clearly confirming the physiological significance of DHA-mediated modulation of Slo1+β1 channels (27). In addition to the roles in the cardiovascular system (29), omega-3 fatty acids are also important in other systems. For instance, DHA is essential for normal development and function of the brain (30).…”

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confidence: 70%

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Hoshi

Tian

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Large-conductance Ca 2+ -and voltage-activated K + (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.K Ca 1.1 | fish oil | lipids

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confidence: 70%

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Hoshi

Tian

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, EPA and DHA have been shown to improve dyslipidaemia, to lower blood pressure and heart rate, to reduce inflammation, and to improve vascular function (125)(126)(127) . An alternative (n-3) PUFA is Table 4.…”

Section: Plant and Marine N-3 Fatty Acidsmentioning

confidence: 99%

ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

2012

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ApoE is a key protein in lipid metabolism with three major isoforms. ApoE allele frequencies show non-random global distribution especially in Europe with high apoE e3 frequency in the Mediterranean area, whereas the apoE e4 genotype is enriched in Northern Europe. The apoE e4 genotype is one of the most important genetic risk factors for age-dependent chronic diseases, including CVD and Alzheimer's disease (AD). The apoE polymorphism has been shown to impact on blood lipids, biomarkers of oxidative stress and chronic inflammation, which all may contribute to the isoform-dependent disease risk. Studies in mice and human subjects indicate that the apoE e3 but not the apoE e4 genotype may significantly benefit from dietary flavonoids (e.g. quercetin) and n-3 fatty acids. Metabolism of lipid soluble vitamins E and D is likewise differentially affected by the apoE genotype. Epidemiological and experimental evidence suggest a better vitamin D status in apoE e4 than e3 subjects indicating a certain advantage of e4 over e3. The present review aims at evaluation of current data available on interactions between apoE polymorphism and dietary responsiveness to flavonoids, fat soluble vitamins and n-3 fatty acids. Likewise, distinct geographic distribution and chronic disease risk of the different apoE isoforms are addressed.

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“…S1) is considered to promote good health in numerous and diverse ways, potentially protecting the immune, nervous, and cardiovascular systems (1,2). Although large-scale clinical trials using dietary supplements have not yielded unequivocal results (3,4), individuals are advised to consume fish rich in DHA for cardiovascular health (5) and numerous dietary supplements containing derivatives of omega-3 fatty acids are widely available.…”

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confidence: 99%

“…Consumption of oily fish high in DHA such as anchovy, herring, mackerel, and salmon has been suggested to decrease blood pressure in some individuals (1,8,9). A diet supplemented with mackerel has been reported to lower blood pressure in healthy volunteers (10).…”

mentioning

confidence: 99%

Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca ²⁺ -dependent K ⁺ channels

Hoshi

Wissuwa

Tian

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

125

139

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Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA), found abundantly in oily fish, may have diverse health-promoting effects, potentially protecting the immune, nervous, and cardiovascular systems. However, the mechanisms underlying the purported health-promoting effects of DHA remain largely unclear, in part because molecular signaling pathways and effectors of DHA are only beginning to be revealed. In vascular smooth muscle cells, large-conductance Ca 2+ -and voltage-activated K + (BK) channels provide a critical vasodilatory influence. We report here that DHA with an EC 50 of ∼500 nM rapidly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit β1, increasing currents by up to ∼20-fold. The DHA action is observed in cell-free patches and does not require voltage-sensor activation or Ca 2+ binding but involves destabilization of the closed conformation of the ion conduction gate. DHA lowers blood pressure in anesthetized wildtype but not in Slo1 knockout mice. DHA ethyl ester, contained in dietary supplements, fails to activate BK channels and antagonizes the stimulatory effect of DHA. Slo1 BK channels are thus receptors for long-chain omega-3 fatty acids, and these fatty acids-unlike their ethyl ester derivatives-activate the channels and lower blood pressure. This finding has practical implications for the use of omega-3 fatty acids as nutraceuticals for the general public and also for the critically ill receiving omega-3-enriched formulas.fish oil | lipids | K Ca 1.1 | immunonutrition

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Cardiovascular effects of marine omega-3 fatty acids

Cited by 462 publications

References 99 publications

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca ²⁺ -dependent K ⁺ channels

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Cardiovascular effects of marine omega-3 fatty acids

Cited by 462 publications

References 99 publications

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA

ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca 2+ -dependent K + channels

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Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca ²⁺ -dependent K ⁺ channels