Shireen Al-Asfoor (Oman)

Imperial College London National Heart & Lung Institute
Ms. Shireen Al-Asfoor began her formal scientific education in the United Kingdom where she obtained her bachelor’s degree in Pharmacology and Physiology at Medway School of Pharmacy which is a joint program between the Universities of Kent and Greenwich. She then completed her Master of Research in Drug Discovery and Development: Multidisciplinary Science for Next Generation Therapeutics at Imperial College London. Her thesis title was: “Understanding How Omega-3 Fatty Acids Found in Fish Oil Protect the Cardiovascular System” supervised by Professor Jane Mitchell, Dr Nicholas Kirkby and Dr Preston Mason in the Cardiothoracic Pharmacology group under the department of National Heart & Lung Institute. The results from this multi-disciplinary research revealed novel cardioprotective mechanisms of an omega-3 fatty acid, eicosapentaenoic acid (EPA), through iNOS inhibition and modulation of prostaglandin synthesis in macrophages. The results showed a pronounced anti-inflammatory effect of EPA related to the expression and/or activities of both COX and iNOS that were not observed with docosahexaenoic acid (DHA). These novel effects of EPA in macrophages provide mechanistic support for recent clinical trials (REDUCE-IT) and has implications for treatment of cardiovascular disease and viral infections.

Author Of 1 Presentation

O036 - Differential Effects of Omega-3 Fatty Acids on Lipopolysaccharide (LPS)-induced Macrophage Activation in Combination with COX inhibition (ID 138)

Session Type
Lipoproteins and Metabolism
Session Time
12:30 - 14:00
Date
Tue, 01.06.2021
Room
Hall B (Live Q&A)
Lecture Time
13:00 - 13:08

Abstract

Background and Aims

Macrophages contribute to chronic diseases by promoting inflammation. Macrophage activation results in increased inducible nitric oxide synthase (iNOS) expression which can be modulated by cyclooxygenase (COX) activity. As both a substrate and potential inhibitor of COX activity, the omega-3 fatty acid EPA may modulate iNOS activity. We investigated the effect of EPA and DHA on iNOS activity in LPS-activated macrophages.

Methods

Murine J774 macrophages were pretreated with vehicle, EPA or DHA over a range of concentrations (1.9µM-50µM) during a challenge with lipopolysaccharide (LPS) at 1.0 µg/ml in DMEM supplemented with 1% FCS. After 24 hr, iNOS activity was assessed by nitrite production using the Griess assay. As a positive control, nitrite measurements with EPA and DHA were compared in combination with the COX inhibitor diclofenac at 100 µM.

Results

Macrophage treatment with LPS increased nitrite levels. EPA treatment reduced LPS-induced nitrite production in a concentration-dependent manner with statistically significant reductions (Figure 1). The inhibitory effects of EPA on iNOS activity were significantly (p<0.0001; two-way ANOVA with Sidak’s multiple comparisons test, n=9) enhanced at all concentrations in the presence of diclofenac. By contrast, DHA did not significantly reduce LPS induced iNOS activity either in the absence or presence of diclofenac.epa inhibits lps-induced nitrite release that is enhanced with diclofenac.jpg

Conclusions

Our observations that EPA but not DHA reduced macrophage iNOS activity may contribute to our understanding of the reduced cardiovascular events as reported in the REDUCE-IT trial with an EPA only formulation. The ability of EPA to modulate macrophage activity has therapeutic implications for patients with cardiovascular risk.

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Presenter of 1 Presentation

O036 - Differential Effects of Omega-3 Fatty Acids on Lipopolysaccharide (LPS)-induced Macrophage Activation in Combination with COX inhibition (ID 138)

Session Type
Lipoproteins and Metabolism
Session Time
12:30 - 14:00
Date
Tue, 01.06.2021
Room
Hall B (Live Q&A)
Lecture Time
13:00 - 13:08

Abstract

Background and Aims

Macrophages contribute to chronic diseases by promoting inflammation. Macrophage activation results in increased inducible nitric oxide synthase (iNOS) expression which can be modulated by cyclooxygenase (COX) activity. As both a substrate and potential inhibitor of COX activity, the omega-3 fatty acid EPA may modulate iNOS activity. We investigated the effect of EPA and DHA on iNOS activity in LPS-activated macrophages.

Methods

Murine J774 macrophages were pretreated with vehicle, EPA or DHA over a range of concentrations (1.9µM-50µM) during a challenge with lipopolysaccharide (LPS) at 1.0 µg/ml in DMEM supplemented with 1% FCS. After 24 hr, iNOS activity was assessed by nitrite production using the Griess assay. As a positive control, nitrite measurements with EPA and DHA were compared in combination with the COX inhibitor diclofenac at 100 µM.

Results

Macrophage treatment with LPS increased nitrite levels. EPA treatment reduced LPS-induced nitrite production in a concentration-dependent manner with statistically significant reductions (Figure 1). The inhibitory effects of EPA on iNOS activity were significantly (p<0.0001; two-way ANOVA with Sidak’s multiple comparisons test, n=9) enhanced at all concentrations in the presence of diclofenac. By contrast, DHA did not significantly reduce LPS induced iNOS activity either in the absence or presence of diclofenac.epa inhibits lps-induced nitrite release that is enhanced with diclofenac.jpg

Conclusions

Our observations that EPA but not DHA reduced macrophage iNOS activity may contribute to our understanding of the reduced cardiovascular events as reported in the REDUCE-IT trial with an EPA only formulation. The ability of EPA to modulate macrophage activity has therapeutic implications for patients with cardiovascular risk.

Hide