Parisa Zarei Shargh

Asie Ahmadi Hoseini

Fariba Mohajer

Mashhad University Of Medical Science

Omega-3 poly unsaturated fatty acids

Flaxseed, canola, walnut,

soybean oil, seeweed, kidney

beans

Sea food: anchovy, herring, salmon,mackerel,bluefish, sardin,

trout,tilefish,swordfish,tu

na

Predominantyby

endogenous metabolism rather than

diet

0.2% -

8%

0%-

4%

Yang etal.2009

Omega3 response

to inflammation

Indirect

Antithrombotic and

antiinflammatory

effect

Inflammation

resolving

Direct Regulation of

transcription factor

Suppresion of APRs

Change in memberane lipid

composition

Mechanism of Omega3 PUFA

on cardiovascular health

Caterina R.NEJM.2011

Hydro-peroxyecosatetraenoic acid

Epoxy ecosatrionic

acid

Inhibiting expression of

chemokines, VCAM, ICAM, NF-KP

activation,nuetrophilmigration

Lower macrophage-produced cytokines including IL-1α ,IL-

1β, TNFα,MCP1

Inhibition of neutrophil

transmigration and infiltration

Reduceneutrophil recruiment

Adkins etal.2010

Family Drived form Main effect

Lipoxins Arachidonic Acid (AA), especially inpresence of omega-3 EPA and DHAfrom fish oil

Potent triggers that end acute inflammation

Resolvins Omega-3 EPA and DHA from fish oil

Novel Anti-Inflammatory and Inflammation Resolving Mediators

Protectins Omega-3 DHA from fish oil

Especially active in protecting brain tissue by promptly endingacute inflammation; synthesis of Protectinsbegins immediatelyafter acute injury.

Serhan CN. 2008

APRs Acute-phase reactants are proteins whose concentrations increaseor decrease by 25% during injury or inflammatory states.

C3 component of complements, haptoglobin,ferritin, α-1 antitrypsin, albumin, transferrin, apolipoprotein CIII (ApoCIII), CRP, fibrinogen and SAA.

NF-κB As a major transcription factor in inflammatory responses,nuclear factor B (NF-B) is involved in the regulation ofinflammatory and immune genes, apoptosis and cell proliferation.

NF-B is the general name for a family of transcriptionfactors consisting of 5 members: p65 (RelA), c-Rel, RelB,NF-B1 (p50 and its precursor p105), and NF-B2 (p52 andits precursor p100).

Toll-like receptor 4(TLR4) a key receptor in the development of atherosclerosisToll-like receptor 4 generates downstream signaling cascadesthat lead to NF-κBactivation and expression of COX-2, inflammatorycytokines and adhesion molecules.

Peroxisome proliferator-activated receptors)

PPAR(

have also been shown to affect the NF-B signaling pathway. PPARα has strong anti-inflammatory properties.

PPARα, PPARγ and PPARδ,

Menno P.J .2005

NF-B activation. Two NF-B activation cascades can be discriminated.

The classical NF-B activation pathway (left) involves the activation of the IKK complex with the subsequent degradation of IB and nuclear translocation of the NF-B dimer.

The alternative NF-B activation cascade (right) is mediated through IKK1 and results in the processing of p100 to p52, resulting in the nuclear transfer of the relB-p52 dimer. Ub indicatesubiquitination.

Mozaffarian, D J2011

w-3 PUFA prevents CVD by changing properties of cell

membrane….

Alters the content of the membrane PL FA.

Alter microdomain lipid composition

Membrane effects on ion channel conductance

Yuriko Akins et al.2010

Lipid rafts Caveolae Signal transduction

endocytosisoncogenesisUptake of pathogenic bacteria & certain viruses

When n-3 PUFA is introduced, the microdomain lipid composition is altered: the sphingomyelin content in lipid rafts and the cholesterol and caveolin in caveolae are reduced .

Yuriko Akins et al.2010

W-3 PUFAs prevents arrhythmias through multiple mechanisms :

1.Mechanismis that n-3 PUFA reduced membrane electrical

excitability and activity of voltage-dependent Na+ channels in

cardiomyocytes.

This is mediated through an increase in the threshold of depolarizing

current required to initiate an action potential and by prolonging the

refractory period following an action potential.

2. By cytosolic free Ca2+ variability exhibited a modulatory action on L-

type Ca2+ channels, which resulted in lowered cytosolic free Ca2+ and

Ca2+ influx rate however,

AA led to Ca2+ overload during a period of ischemic stress .

Yuriko Akins et al.2010

Decreasing endothelial activation

Endothelial cells ICAM-1VCAM-1E-selectinP-selectin

Are involved in leukocyte recruitment and platelet adhesion during thrombosis and inflammation and also contribute to early phases of atherogenesis .

PUFA have been shown to inhibit the production of inflammatory

cytokines that activate the endothelium .

N-3 PUFA Decreasing the expression of adhesion molecule in human monocytes and murine macrophages.

Yuriko Akins et al.2010

Vasorelaxant effect of DHA

The vasorelaxant effect of DHA has been attributed to the decreases in Ca2+ influx in VSMCs .

N-3 PUFA can modify eicosanoid production to favor vasodilation and antithrombotic actions.

N-3 PUFAs increase endothelium-dependent relaxation through an enhancement of NO release.NO inhibits platelet aggregation and adhesion,

leukocyte adhesion and smooth muscle cell proliferation .

Logan Bronwell.2012

Exaggerated VSMC growth results in arterial damage and is an important component in the pathogenesis of atherosclerosis.

DHA to a lesser extent, can affect vascular function through the inhibition in VSMC growth and proliferation at various steps of the signal transduction pathway of growth factors .

Darshan S. Kwlley and Yuriko Adkins.2012

Elevated fasting and postprandial plasma TG levels increase inflammation and are independent risk factors for CVD.

DHA supplementation reduced both the fasting and postprandial TGs by more than 25% hypertriglyceridemic men .

DHA also decreased the concentrations of atherogenic small dense LDL particles, total LDL particles and the remnant chylomicron particles.

Decrease Apo CIII , SREBP-1c activity ,FA substrates for lipogenesis

Increase LPL ,FXR ,PPARα-induced oxidation ,Apo CII ,VLDL-receptor gene expression

Darshan S. Kelley et al .2009

Dariush Mozaffarian .2011

Arrhythmia Decrease Two-series PG

Surface membrane electrical excitability :

Activity of voltage-dependent Na+ channels

Ca2+ release channels and intracellular Ca2+

Increase Three-series PG

Stimulation Proresolving mediators

Increase Lipoxins, resolvins and protectins

Stabilization of atherosclerotic plaques

Decrease Infiltration of monocytes into the plaques

Activity of cells, that is, macrophages within the plaques

Increase Incorporation of n-3 PUFA into plaques

TG & cholesterol lowering Decrease Apo CIII , SREBP-1c activity ,FA substrates for lipogenesis

Increase LPL ,FXR ,PPARα-induced oxidation ,Apo CII ,VLDL-receptor gene expression

Changes in membrane lipid composition

Decrease Sphingomyelin content in lipid rafts

Cholesterol and caveolin in caveolae

Increase Membrane fluidity

Result