Epoxyeicosatrienoic Acids, TRP Channels, and Intracellular Ca
            <sup>2+</sup>
            in the Vasculature

Larsen, Brandon T.; Zhang, David X.; Gutterman, David D.

doi:10.1161/atvbaha.107.155341

Cited by 9 publications

(3 citation statements)

References 24 publications

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“…A second major pathway covered is the CYP-epoxygenase pathway, whose fatty acid epoxides have potent vaso-protective activities, including protection from both septic [28] and hypertensive vascular diseases [29] . Fatty acid epoxides act on resistance vessels to produce an endothelial hyperpolarizing effect [30] , and EC 50 estimates are available in the same model for AA-, EPA- and DHA-epoxides [31] , [32] . These studies offer a means to estimate the impact of P-OM3 treatment.…”

Section: Discussionmentioning

confidence: 99%

Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic, Statin-Treated Subjects

et al. 2014

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BackgroundOxylipins mediate inflammation, vascular tension, and more. Their presence in lipoproteins could explain why lipoproteins mediate nearly identical activities.MethodsTo determine how oxylipins are distributed in the lipoproteins of hypertriglyceridemic subjects, and whether omega-3 fatty acids alter them in a manner consistent with improved cardiovascular health, we recruited 15 dyslipidemic subjects whose levels of low density lipoprotein cholesterol (LDL-C) were at goal but who remained hypertriglyceridemic (200–499 mg/dL). They were treated them with the indicated dose of 4 g/d omega-3 acid ethyl esters (P-OM3) for 8 weeks. Measured oxylipins included mid-chain alcohols (HETEs, HEPEs and HDoHEs), ketones (KETEs), epoxides (as EpETrEs, EpETEs, and EpDPEs).ResultsAt baseline, arachidonate-oxylipins (HETEs, KETEs, and EpETrEs) were most abundant in plasma with the greatest fraction of total abundance (mean |95% CI|) being carried in high density lipoproteins (HDL); 42% |31, 57| followed by very low density lipoproteins (VLDL); 27% |20, 36|; and LDL 21% |16, 28|. EPA- and DHA-derived oxylipins constituted less than 11% of total. HDL carried alcohols and epoxides but VLDL was also rich in ketones. Treatment decreased AA-derived oxylipins across lipoprotein classes (−23% |−33, −12|, p = 0.0003), and expanded EPA−(322% |241, 422|, p<0.0001) and DHA-derived oxylipins (123% |80, 176|, p<0.0001).ConclusionsEach lipoprotein class carries a unique oxylipin complement. P-OM3 treatment alters the oxylipin content of all classes, reducing pro-inflammatory and increasing anti-inflammatory species, consistent with the improved inflammatory and vascular status associated with the treatment.Trial RegistrationClinicalTrials.gov NCT00959842

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Section: Discussionmentioning

confidence: 99%

Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic, Statin-Treated Subjects

et al. 2014

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“…L-NAME (L-N 6 -nitroarginine methyl ester), an analog of arginine that inhibits nitric oxide production, is expected to potentiate the bradykinin concentration-constrictor response curves because the dilation is prevented [19][20][21][22][23][24][25]35]. As described for group 1, control dose-response curves to bradykinin were obtained at 11 and16 ml/min.…”

Section: Group 2 L-name Treatmentmentioning

confidence: 99%

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

Jiménez-Corona¹,

Espinosa‐Tanguma²,

Knabb³

et al. 2017

J Transl Sci

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Studies in perfused hearts show that flow-sensitive G-protein coupled receptors are lectinic suggesting that flow exerts its effects by modulating the interaction between endothelial surface layer oligosaccharides and lectinic transmembrane G-protein coupled receptors. To test this hypothesis guinea pig carotid arteries were perfused with Krebs-Henseleit at 11 or 16 ml/min. The effects of flow on the contraction induced by stimulating the bradykinin receptor were determined using the flow-induced changes of bradykinin concentration-vascular response curves. Flow effects on the bradykinin receptor were studied in four independent groups; in Groups 1 and 2 (controls) the endothelial surface layer glyosidic composition was not altered, in Group 3 an oligosaccharide polymer that lectinically and irreversibly binds to endothelial surface layer was infused, and in Group 4 endothelial surface layer heparinic were hydrolyzed. Results show that an increase in flow from 11 to 16 ml/min shifted the vascular response curve of bradykinin upward and to the left. Similar results were obtained with endothelial surface layer oligosaccharide polymer binding and heparinic removal but elevation of flow from 11 to 16 ml/min had no effect. Thus, the flow dependence of the lectinic bradykinin receptor depends on its ability to interact with the oligosaccharide environment and heparinic groups.

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“…EETs not only activate endothelial IK Ca and SK Ca but also open myocyte large-conductance K Ca (BK Ca ) to relax vessels [ 49 ]. The opening of IK Ca and SK Ca and the production of EETs also depend on [Ca 2+ ] i rise in endothelial cells [ 48 , 50 ].…”

Section: Role Of Endothelial Ion Channels In No and Edhf Pathwaysmentioning

confidence: 99%

Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

Yang

et al. 2014

BioMed Research International

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Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K+ channels and Ca2+-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K+ channels, that is, KATP and KCa, and Ca2+-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K+ and TRP channels for myocardial protection during cardiac surgery.

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Epoxyeicosatrienoic Acids, TRP Channels, and Intracellular Ca ²⁺ in the Vasculature

Cited by 9 publications

References 24 publications

Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic, Statin-Treated Subjects

Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic, Statin-Treated Subjects

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

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Epoxyeicosatrienoic Acids, TRP Channels, and Intracellular Ca 2+ in the Vasculature

Cited by 9 publications

References 24 publications

Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic, Statin-Treated Subjects

Effect of Omega-3 Fatty Acid Ethyl Esters on the Oxylipin Composition of Lipoproteins in Hypertriglyceridemic, Statin-Treated Subjects

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

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Product

Resources

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Epoxyeicosatrienoic Acids, TRP Channels, and Intracellular Ca ²⁺ in the Vasculature