Relationship between the omega-3 index and specialized pro-resolving lipid mediators in patients with peripheral arterial disease taking fish oil supplements

Schaller, Melinda S.; Zahner, Greg J.; Gasper, Warren J.; Harris, William S.; Conte, Michael S.; Hills, Nancy K.; Grenon, S. Marlene

doi:10.1016/j.jacl.2017.06.011

Cited by 21 publications

(14 citation statements)

References 38 publications

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“…Long-term omega-3 supplementation increases EPA and DHA content in erythrocyte phospholipids that is used as a marker of omega-3 intake, namely, the omega-3 index ( 51 ). Increasing the omega-3 index positively correlates with plasma SPM precursors in patients with peripheral arterial disease ( 52 ). Erythrocytes are known to enhance the formation of human neutrophil 5-LOX products ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Resolution metabolomes activated by hypoxic environment

2019

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Targeting hypoxia-sensitive pathways in immune cells is of interest in treating diseases. Here, we demonstrate that physiologic hypoxia (1% O2), as encountered in bone marrow and spleen, accelerates human M2 macrophage efferocytosis of apoptotic-neutrophils and senescent erythrocytes via lipolysis-dependent biosynthesis of specialized pro-resolving mediators (SPMs), i.e. resolvins, protectins, maresins and lipoxin. SPM-production was enhanced via hypoxia in M2 macrophages interacting with neutrophils and erythrocytes enabling structural elucidation of a novel eicosapentaenoic acid (EPA)–derived resolvin, resolvin E4 (RvE4) that stimulates efferocytosis of senescent erythrocytes and more potently than aspirin in mouse hemorrhagic exudates. In hypoxia, glycolysis inhibition enhanced neutrophil RvE4-SPM biosynthesis. Human macrophage-erythrocyte co-incubations in physiologic hypoxia produced RvE4-SPM from erythrocyte stores of omega-3 fatty acids. These results indicate that hypoxic environments, including bone marrow and spleen as well as sites of inflammation, activate SPM-biosynthetic circuits that in turn stimulate resolution and clearance of senescent erythrocytes and apoptotic neutrophils.

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Section: Discussionmentioning

confidence: 99%

Resolution metabolomes activated by hypoxic environment

2019

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“…The O3I has been reported to be positively correlated with dietary intake of EPA and DHA (Harris et al, ) and results in increases in downstream SPM intermediates (Schaller et al, ). Previous studies have identified that patients with PAD have poor dietary intake of n‐3 PUFA and other nutrients that may affect disease progression or outcomes (Nosova et al, ).…”

Section: Discussionmentioning

confidence: 99%

Peripheral Artery Disease Is Associated with a Deficiency of Erythrocyte Membrane n‐3 Polyunsaturated Fatty Acids

Ramirez

Spaulding

Khetani

et al. 2019

Lipids

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Population‐based data suggest that individuals who consume large dietary amounts of n‐3 polyunsaturated fatty acids (PUFA) have lower odds of peripheral artery disease (PAD); however, clinical studies examining n‐3 PUFA levels in patients with PAD are sparse. The objective of this study is to compare erythrocyte membrane fatty acid (FA) content between patients with PAD and controls. We conducted a cross‐sectional study of 179 vascular surgery outpatients (controls, 34; PAD, 145). A blood sample was drawn and the erythrocyte FA content was assayed using capillary gas chromatography. We calculated the ratio of the n‐3 PUFA eicosapentaenoic acid (EPA) to the n‐6 PUFA arachidonic acid (ARA) as well as the omega‐3 index (O3I), a measure of erythrocyte content of the n‐3 PUFA, EPA, and docosahexaenoic acid (DHA), expressed as a percentage of total erythrocyte FA. Compared with controls, patients with PAD smoked more and were more likely to have hypertension and hyperlipidemia (p < 0.05). Patients with PAD had a lower mean O3I (5.0 ± 1.7% vs 6.0 ± 1.6%, p < 0.001) and EPA:ARA ratio (0.04 ± 0.02 vs 0.05 ± 0.05, p < 0.001), but greater mean total saturated fats (39.5 ± 2.5% vs 38.5 ± 2.6%, p = 0.01). After adjusting for several patient characteristics, comorbidities, and medications, an absolute decrease of 1% in the O3I was associated with 39% greater odds of PAD (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.03–1.86, and p = 0.03). PAD was associated with a deficiency of erythrocyte n‐3 PUFA, a lower EPA:ARA ratio, and greater mean total saturated fats. These alterations in FA content may be involved in the pathogenesis or development of poor outcomes in PAD.

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“…Adapted with permission from ref. 48 ship between changes in the O3I and these SPM pathway markers (109). However, downstream bioactive SPMs were sparsely detected in plasma, and measures of endothelial function and systemic inflammation were unchanged following the 1-month intervention.…”

Section: Translation: Developing a Platform For Pro-resolving Vasculamentioning

confidence: 99%

Pro-resolving lipid mediators in vascular disease

Conte¹,

Desai²,

Wu³

et al. 2018

Journal of Clinical Investigation

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Unresolved inflammation is central to the pathophysiology of commonly occurring vascular diseases such as atherosclerosis, aneurysm, and deep vein thrombosis - conditions that are responsible for considerable morbidity and mortality. Surgical or catheter-based procedures performed on affected blood vessels induce acute-on-chronic inflammatory responses. The resolution of vascular inflammation is an important driver of vessel wall remodeling and functional recovery in these clinical settings. Specialized pro-resolving lipid mediators (SPMs) derived from omega-3 polyunsaturated fatty acids orchestrate key cellular processes driving resolution and a return to homeostasis. The identification of their potent effects in classic animal models of sterile inflammation triggered interest in their vascular properties. Recent studies have demonstrated that SPMs are locally synthesized in vascular tissues, have direct effects on vascular cells and their interactions with leukocytes, and play a protective role in the injury response. Early translational work has established the potential for SPMs as vascular therapeutics, and as candidate biomarkers in vascular disease. Further investigations are needed to understand the molecular and cellular mechanisms of resolution in the vasculature, to improve tools for clinical measurement, and to better define the potential for "resolution therapeutics" in vascular patients.

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Relationship between the omega-3 index and specialized pro-resolving lipid mediators in patients with peripheral arterial disease taking fish oil supplements

Cited by 21 publications

References 38 publications

Resolution metabolomes activated by hypoxic environment

Resolution metabolomes activated by hypoxic environment

Peripheral Artery Disease Is Associated with a Deficiency of Erythrocyte Membrane n‐3 Polyunsaturated Fatty Acids

Pro-resolving lipid mediators in vascular disease

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