The Potential of Docosahexaenoic Acid (DHA) in SARS-CoV-2 Management: DHA Reduces ACE2 Levels in Endothelial Cells

Abstract Objectives Angiotensin-converting enzyme 2 (ACE2) is a transmembrane protein located on the surface of endothelial cells that promotes vasodilation by promoting the hydrolysis of angiotensin II. However, ACE2 also serves as the cellular receptor for SARS-CoV-2. Infection by SARS-CoV-2 can promote endothelial dysfunction which in turn is associated with greater infection severity. Long chain omega-3 fatty acids (n3 PUFA) like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are reported to prevent endothelial dysfunction. Thus, we hypothesize that treatment with n3 PUFA may suppress the actions of SARS-CoV-2 on endothelial cells, potentially through endothelial ACE2. The objective of the study was therefore to investigate whether changes in ACE2 levels occur as part of the endothelial response to n3 PUFA treatment. Methods Male fa/fa Zucker rats were randomised into 4 PUFA-based diet groups: α-linoleic acid (ALA), EPA, DHA, and linoleic acid (LA), for 8 weeks. EA.hy926 cells were cultured to sub-confluent and quiescent states and treated with various doses of DHA, EPA, and ALA for 8 or 24 h. ACE2 levels in tissues and cells were quantified by Western blotting. Results In contrast to ALA and EPA, DHA treatment significantly reduced ACE2 levels in rat heart, aorta, and kidney but not lungs after 8 weeks of diet intervention. EPA only showed this reduction compared to ALA in kidney. Interestingly, when applied to human endothelial cells in culture, DHA decreased ACE2 levels of growing EA.hy926 cells even at relatively low doses, but no significant effect was observed in quiescent cells. EPA also had an effect, but only at an extremely high dose. Conclusions DHA reduced ACE2 levels in key organs and human endothelial cells, which should produce beneficial effects by lowering the susceptibility of cells to SARS-CoV-2. Funding Sources St Boniface Hospital Foundation - Research Without Borders and University of Manitoba - GETS

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OMEGA-3 FATTY ACID EICOSAPENTAENOIC ACID (EPA), BUT NOT DOCOSAHEXAENOIC ACID (DHA), IMPROVED NITRIC OXIDE BIOAVAILABILITY IN HUMAN ENDOTHELIAL CELLS

Canadian Journal of Cardiology ◽

10.1016/j.cjca.2020.07.020 ◽

2020 ◽

Vol 36 (10) ◽

pp. S3-S4

Author(s):

S. Sherratt ◽

P. Mason ◽

H. Dawoud ◽

D. Bhatt ◽

T. Malinski

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Fatty Acid ◽

Docosahexaenoic Acid ◽

Eicosapentaenoic Acid ◽

Omega 3 ◽

Human Endothelial Cells ◽

Omega 3 Fatty Acid ◽

Nitric Oxide Bioavailability

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Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells

10.21203/rs.3.rs-50793/v2 ◽

2020 ◽

Author(s):

Aysan Eslami Abriz ◽

Reza Rahbarghazi ◽

Alireza Nourazarian ◽

Çıgır Biray Avci ◽

Soltan Ali Mahboob ◽

...

Keyword(s):

Fatty Acids ◽

Endothelial Cells ◽

Docosahexaenoic Acid ◽

Palmitic Acid ◽

Pcr Array ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Human Endothelial Cells ◽

Array Analysis ◽

Tnf Α

Abstract Background: Atherosclerosis is touted as one of the most critical consequences of diabetes mellitus indicated by local inflammation of endothelial cells. The Effect of Omega 3 fatty acids, mainly docosahexaenoic acid (DHA), has been investigated in cells after exposure to high doses of lipids. The current experiment aimed to address the modulatory effects of docosahexaenoic acid and insulin in palmitic-treated human endothelial cells. Methods: Human umbilical vein endothelial cells were treated with 1mM palmitic acid, 50μM insulin, 50μM docosahexaenoic acid, and their combination for 48 hours. Cell survival rate and apoptosis were measured using MTT and flow cytometry assays. The Griess assay detected NO levels. Protein levels of TNF-α, IL-6, and NF-κB were studied using ELISA and immunofluorescence imaging. The expression of genes participating in atherosclerosis was monitored using PCR array analysis. Results: Oil Red O staining showed the inhibitory effect of DHA and insulin to reduce the intracellular accumulation of palmitic acid. Both DHA and Insulin blunted palmitic acid detrimental effects on HUVECs indicated by an increased survival rate (p<0.05). The percent of apoptotic cells was decreased in palmitic-treated cells received insulin and DHA compared to palmitic-treated group (p<0.05). Based on our data, DHA and Insulin diminished the production of all inflammatory cytokines, TNF-α, IL-6, and NF-κB, in palmitic-treated cells (p<0.05). Similar to these data, NO production was also decreased in all groups treated with insulin and DHA compared to the palmitic-treated cells (p<0.05). PCR array analysis revealed the modulatory effect of DHA and insulin on the expression of atherosclerosis-related genes pre-treated with palmitic acid compared to the control group (p<0.05). Conclusion: DHA and Insulin could alter the dynamic growth and dysfunctional activity of human endothelial cells after treatment with palmitic acid. Taken together, Omega 3 fatty acids, along with insulin, could dictate specific cell behavior in endothelial cells in vitro

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Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells

Journal of Inflammation ◽

10.1186/s12950-021-00277-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Aysan Eslami Abriz ◽

Reza Rahbarghazi ◽

Alireza Nourazarian ◽

Çıgır Biray Avci ◽

Soltan Ali Mahboob ◽

...

Keyword(s):

Fatty Acids ◽

Endothelial Cells ◽

Docosahexaenoic Acid ◽

Palmitic Acid ◽

Pcr Array ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Human Endothelial Cells ◽

Array Analysis ◽

Tnf Α

Abstract Background Atherosclerosis is touted as one of the most critical consequences of diabetes mellitus indicated by local inflammation of endothelial cells. The Effect of Omega 3 fatty acids, mainly docosahexaenoic acid (DHA), has been investigated in cells after exposure to high doses of lipids. The current experiment aimed to address the modulatory effects of docosahexaenoic acid and insulin in palmitic-treated human endothelial cells. Methods Human umbilical vein endothelial cells were treated with 1 mM palmitic acid, 50 μM insulin, 50 μM docosahexaenoic acid, and their combination for 48 h. Cell survival rate and apoptosis were measured using MTT and flow cytometry assays. The Griess assay detected NO levels. Protein levels of TNF-α, IL-6, and NF-κB were studied using ELISA and immunofluorescence imaging. The expression of genes participating in atherosclerosis was monitored using PCR array analysis. Results Oil Red O staining showed the inhibitory effect of DHA and insulin to reduce the intracellular accumulation of palmitic acid. Both DHA and Insulin blunted palmitic acid detrimental effects on HUVECs indicated by an increased survival rate (p < 0.05). The percent of apoptotic cells was decreased in palmitic-treated cells received insulin and DHA compared to palmitic-treated group (p < 0.05). Based on our data, DHA and Insulin diminished the production of all inflammatory cytokines, TNF-α, IL-6, and NF-κB, in palmitic-treated cells (p < 0.05). Similar to these data, NO production was also decreased in all groups treated with insulin and DHA compared to the palmitic-treated cells (p < 0.05). PCR array analysis revealed the modulatory effect of DHA and insulin on the expression of atherosclerosis-related genes pre-treated with palmitic acid compared to the control group (p < 0.05). Conclusion DHA and Insulin could alter the dynamic growth and dysfunctional activity of human endothelial cells after treatment with palmitic acid. Taken together, Omega 3 fatty acids, along with insulin, could dictate specific cell behavior in endothelial cells in vitro.

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Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells

10.21203/rs.3.rs-50793/v1 ◽

2020 ◽

Author(s):

Aysan Eslami Abriz ◽

Reza Rahbarghazi ◽

Alireza Nourazarian ◽

Çıgır Biray Avci ◽

Soltan Ali Mahboob ◽

...

Keyword(s):

Endothelial Cells ◽

Docosahexaenoic Acid ◽

Palmitic Acid ◽

Pcr Array ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Human Endothelial Cells ◽

Array Analysis ◽

Cell Survival Rate ◽

Tnf Α

Abstract Background: Atherosclerosis is touted as one of the most critical consequences of diabetes mellitus indicated by local inflammation of endothelial cells. The Effect of Omega 3 fatty acids, mainly docosahexaenoic acid (DHA), has been investigated in cells after exposure to high doses of lipids. The current experiment aimed to address the modulatory effects of docosahexaenoic acid and insulin in palmitic-treated human endothelial cells. Methods: Human umbilical vein endothelial cells were treated with 1mM palmitic acid, 50μM insulin, 50μM docosahexaenoic acid, and their combination for 48 hours. Cell survival rate and apoptosis were measured using MTT and flow cytometry assays. The Griess assay detected NO levels. Protein levels of TNF-α, IL-6, and NF-κB were studied using ELISA and immunofluorescence imaging. The expression of genes participating in atherosclerosis was monitored using PCR array analysis. Results: Oil Red O staining showed the inhibitory effect of DHA and insulin to reduce the intracellular accumulation of palmitic acid. Both DHA and Insulin increased the reduced cell survival rate of cells after exposure to palmitic acid (p<0.05). The percent of apoptotic cells was decreased in palmitic-treated cells received insulin and DHA compared to palmitic-treated group (p<0.05). Based on our data, DHA and Insulin diminished the production of all inflammatory cytokines, TNF-α, IL-6, and NF-κB, in palmitic-treated cells (p<0.05). Similar to these data, NO production was also decreased in all groups treated with insulin and DHA compared to the palmitic-treated cells (p<0.05). PCR array analysis revealed the modulatory Effect of DHA and insulin on the expression of atherosclerosis-related genes pre-treated with palmitic acid compared to the control group (p<0.05). Conclusion: DHA and Insulin could alter the dynamic growth and dysfunctional activity of human endothelial cells after treatment with palmitic acid. Taken together, Omega 3 fatty acids, along with insulin, could dictate specific cell behavior in endothelial cells in vitro.

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Lowering the linoleic acid to alpha-linoleic acid ratio decreases the production of inflammatory mediators by cultured human endothelial cells

Prostaglandins Leukotrienes and Essential Fatty Acids ◽

10.1016/j.plefa.2018.12.001 ◽

2019 ◽

Vol 141 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Christian S. Bork ◽

Ella J. Baker ◽

Søren Lundbye-Christensen ◽

Elizabeth A. Miles ◽

Philip C. Calder

Keyword(s):

Endothelial Cells ◽

Linoleic Acid ◽

Inflammatory Mediators ◽

Human Endothelial Cells ◽

Acid Ratio

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Suppressive Effects of the Gynura bicolor Ether Extract on Endothelial Permeability and Leukocyte Transmigration in Human Endothelial Cells Induced by TNF-α

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9413724 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Shu-Ling Hsieh ◽

Jyh-Jye Wang ◽

Kuan-Hua Su ◽

Ying-Lan Kuo ◽

Shuchen Hsieh ◽

...

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Far East ◽

Endothelial Permeability ◽

Intercellular Adhesion Molecule ◽

Ether Extract ◽

Human Endothelial Cells ◽

Tnf Α ◽

Ea.Hy926 Cells ◽

Gynura Bicolor

Gynura bicolor (Roxb. and Willd.) DC (G. bicolor) is generally used as a dietary vegetable and traditional herb in Taiwan and the Far East. G. bicolor exerts antioxidant and anti-inflammatory effects and regulates blood lipids and cholesterol. However, the effects of G. bicolor on endothelial transmigration and atherosclerosis are not clear. The present study investigated the effects of G. bicolor on endothelial permeability and transmigration in human endothelial cells. We prepared G. bicolor ether extract (GBEE) for use as the experimental material. Under TNF-α stimulation, HL-60 cell adherence to EA.hy926 cells, the shape of EA.hy926 cells, and the expression of adhesion molecules and transmigration-related regulatory molecules were analysed after pretreatment with GBEE for 24 h. GBEE inhibited leukocyte adhesion to endothelial cells, reduced intercellular adhesion molecule-1 (ICAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) expressions, and decreased endothelial monolayer permeability. GBEE also reduced paracellular transmigration by reducing the levels of reactive oxygen species (ROS), Src phosphorylation, and vascular endothelial-cadherin (VE-cadherin) phosphorylation. GBEE reduced transcellular migration via inhibition of Ras homolog family member A (RhoA) and Rho-associated protein kinase (ROCK) expression and phosphorylation of the ezrin-radixin-moesin (ERM) protein. Incubation of EA.hy926 cells with GBEE for 8 h and stimulation with TNF-α for 3 h reduced the phosphorylation of the inhibitor of kappa B (IĸB) and DNA-binding activity of nuclear factor-ĸB (NF-ĸB). These results suggest that GBEE has a protective effect against endothelial dysfunction via suppression of leukocyte-endothelium adhesion and transmigration.

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