12/12/2019 Omega Fatty

Acids And Their

Role In The
Prevention Of
Heart Diseases

Sanna Iqbal (18130007)

Aqsa Naseem (18130008)
(Chem 432 Bio Organic
Chemistry)
 Omega fatty acids and their role in the prevention of heart diseases
Omega fatty acids are polyunsaturated essential fatty acids that have their first double bond on
carbon 3 or 6 from free end i-e methyl end or omega end. As they are essential fatty acids they
should be taken in diet as are not synthesized by our body. Their main two types are:
 Omega-6-fatty acids
 Omega-3-fatty acids

Omega-6-fatty acids
Omega-6-fatty acids are polyunsaturated fatty acids that are found in vegetable oils, nuts and seeds
and have first C=C at carbon 6 from methyl end.

List of omega-6-fatty acids:

Omega-3-fatty acids
Omega-3-fatty acids are polyunsaturated fatty acids found in fish oil and have first C=C at
carbon 3 from methyl end.

List of Omega-3-fatty acid:

 Alpha linolenic Acid (ALA)
 Ecosapentaenoic Acid (EPA)
 Docosapentaenoic Acid (DPA)
 Docosahexaenoic Acid (DHA)
Structure of omega-3-fatty acids

Figure : 1 Structures of omega 3 fatty acids

 Mozaffarian, Dariush, and Jason HY Wu. "Omega-3 fatty acids and cardiovascular
disease: effects on risk factors, molecular pathways, and clinical events." Journal of the
American College of Cardiology 58.20 (2011): 2047-2067.
 Pathway of biosynthesis of Omega-3-fatty Acids

 Calder, Philip. "New evidence that omega-3 fatty acids have a role in primary
prevention of coronary heart disease." Journal of Public Health and
Emergency 1.35 (2017).
  Harris, William S., et al. "Omega-3 fatty acids and coronary heart disease risk: clinical
and mechanistic perspectives." Atherosclerosis 197.1 (2008): 12-24.

What are cardiovascular diseases?

Cardiovascular diseases are the diseases which affect our heart or blood vessels. Most common
form of cardiovascular disease is when our blood vessel becomes narrow and the blood supply to
our heart is blocked or interrupted which causes heart attack or heart failure. Our blood contains
cholesterol which is a waxy fat-like substance and triacylglyserides which are also a type of fat,
when the concentration of these two substances increases in our blood it results in the formation
of plaques in our blood vessels which can narrow down them blocking the blood supply to our
heart which can cause heart attack.

Omega-3-fatty acids and cardiovascular diseases

Omega 3 fatty acid can be used for the cardioprotective due to many reasons.
They are following mechanisms:

 Antiarrhythmic effect:
Cell membranes are made up of phospholipids, containing different types of fatty acids. The
length and poly unsaturation of these fatty acids can affect the properties of cell membrane. As
omega-3 PUFAs have many double bonds and long-chain carbons, their incorporation into the
PLs within a membrane can alter its properties and influence the function of various membrane
proteins including the suppression of protein kinase C theta signaling and interleukin (IL)-2
production , and the disruption of dimerization and recruitment of toll-like receptor 4 . Of note,
alteration of the lipid microenvironment in cardiomyocytes through the inclusion of omega-3
PUFAs can modulate ion channel function, leading to anti-arrhythmic effects.

.Figure: 3 The proposed molecular mechanism of cardioprotection by omega-3 PUFAs

 Endo, Jin, and Makoto Arita. "Cardioprotective mechanism of omega-3 polyunsaturated
fatty acids." Journal of cardiology 67.1 (2016): 22-27.
PUFAs when incorporated into the phospholipid bilayer they control membrane ion channels to
prevent lethal arrhythmia. Also omega-3 PUFAs exert anti-inflammatory and anti-fibrotic effects
by modifying NF-κB signaling, the NLRP3 inflammasome, PPARα/γ, GPR120, and TGF-β
signaling.

 Antithrombotic properties:
Thrombotic properties are also shown by Omega 3 fatty acid. Thromboxane A2 and
prostaglandin which cause the platelets aggregation and vasoconstrictions. APA inhibits the
synthesis of these glands. Reactivity and adhesion of platelets are also reduced by the EPA.
When this happens then the bleeding time increases also adherence of platelets to beads
decreases. Fibrinogen level also decreases also have shown other antithrombotic effect.

 Endothelial Function:
Omega 3 fatty acid significantly affect the endothelial function. Human who consumes the fish
oil or fish in their daily life have shown the less oxygen deprived free radical production, which
are mainly produced by the neutrophils. EPA enhanced the nitrous oxide. Bioavailability
increases, when the level of free radical decreases. Patients who consumed the fish oil, there was
significantly improvement in artery flow vasodilation. Reduction in leucocytes also play an
important role in endothelial function.

 Inhibition of Atherosclerotic Plaque:

Macrophages and smooth cells are important for the atherosclerotic development. Platelets
derived growth factor is responsible for the formation of macrophages and smooth cells. This
factor is reduced by the consumption of omega 3 fatty acid.

 The anti-inflammatory effects of omega-3 PUFAs:

Acute and chronic inflammation can lead to various cardiovascular diseases like, myocarditis,
myocardial infarction, aortic dissection, atherosclerosis, and cardiac remodeling. Dietary intake of
omega-3 PUFAs can decrease the circulating concentrations of inflammatory cytokines such
as tumor necrosis factor (TNF), IL-1β, and IL-6, and ameliorate left ventricular functional capacity
in non-ischemic dilated cardiomyopathy.
EPA and DHA can decrease or minimize the expression of inflammation-related genes through
inhibition of NF-κB signaling by blocking IκB phosphorylation or through the nuclear
receptor PPARα/γ . Also omega-3 PUFA is a ligand for GPR120, which reduces both toll-like
receptor 4- and TNF-α-mediated proinflammatory signaling in macrophages.
 Figure: 4 Anti-inflammatory effects of omega-3 PUFAs through mediator balance

The anti-inflammatory effects of omega-3 PUFAs can be summarized as

 Prevention of the conversion of AA into PGs and LTs
 Its ability to function as an alternative substrate to produce less potent mediators.
 Resolvins, protectins, and maresins, are distinct anti-inflammatory and pro-resolving lipid
mediators derived from omega-3 PUFAs.

 Novel bioactive lipid mediators of omega-3 PUFAs:

Omega 3 fatty acids can prevent the conversion of the omega-6 PUFA arachidonic acid (AA)
into pro-inflammatory prostaglandins (PGs) and leukotrienes (LTs), or can serve as an
alternative substrate, producing less potent mediators, such as 3-series PGs
and thromboxanes (TXs) and 5-series LTs. Also reduces the formation of the pro-
thrombotic prostanoid TXA2 from AA. Omega-3 PUFAs can be metabolized to PGI3, which
possesses anti-platelet effects, and TXA3, which does not induce platelet aggregation.
PUFAs cab be oxidized by CYP450 monooxygenase to epoxides, which function as potent lipid
mediators in the cardiovascular system. The epoxyeicosatrienoic acids (EETs) generated from
AA induce vasodilation, stimulate angiogenesis, and protect the heart from ischemia/reperfusion
injury.
Studies have shown that Consumption of fish oil significantly inhibit the LDL and Triglyceride
in liver by lowering the amount of cholesterol and triglyceride. Large consumption of fish oil
has shown that it reduces the cholesterol level in hypertriglyceridemic patients. Fish oil reduced
the level of postprandial lipemia, which is mainly increased by the consumption of the olive oil.
Omega 3 fatty acid seems to decrease the smaller triglycerides unit by increasing the large
cholesterol subtypes.

 Novel beneficial effects of a macrophage-derived EPA metabolite, 18-

HEPE, on cardiac remodeling:
Administration of 18-HEPE(18-hydroxy eicosapentaenoic acid ) can prevent cardiac
dysfunction, macrophage infiltration, and cardiac fibrosis after transverse aortic
constriction (TAC)1 . An EPA metabolite, 18-HEPE, from cardiac macrophages rich in omega-3
PUFAs can prevent cardiac remodeling under pressure overload. Activated cardiac fibroblasts,
namely myofibroblasts, produce pro-inflammatory mediators that facilitate cardiac macrophage
activation. Cardiac fibroblasts can be activated directly by pressure overload or secondarily
by inflammatory mediators released from activated inflammatory cells. EPA-enriched
macrophages can generate an 18-HEPE-rich milieu in the heart, thereby discontinuing the
profibrotic feed-forward loop that can be involved in the development of cardiac fibrosis under
pressure overload.

Figure: 5 Difference between omega 3 fatty acid rich and poor milieu
 These effects of omega 3 fatty acids can be summarized as following:

Figure : 2 Physiological effect of omega-3-polyunsaturated fatty acids which can reduce

risk of cardiovascular diseases
 Mozaffarian, Dariush, and Jason HY Wu. "Omega-3 fatty acids and cardiovascular
disease: effects on risk factors, molecular pathways, and clinical events." Journal of the
American College of Cardiology 58.20 (2011): 2047-2067.
 Similarly affects of DPA and DHA intake can be summarized as following:

Table : 1 Effects of DPA and DHA intake

Side affects of omega-3-fatty acids:

Omega-3-fatty acids are beneficial for our health if taken in diet or as a supplement in
appropriate amount, if taken in excess can cause some side affects7 like:
 High Blood sugar
 Bleeding that can be nosebleeding or gums bleeding
 Low blood pressure
 Diarrhea
 Acid reflux
 Stroke
 Vitamin A toxicity
 Insomnia
Upto 5000 mg of omega-3-fatty acids per day are considered safe. Recommended daily dosage
of omega-3-fatty acids by different health organizations is as following:
 Table: 2 Recommended omega-3-fatty acid dosage by different health organizations

References
1. Endo, Jin, and Makoto Arita. "Cardioprotective mechanism of omega-3 polyunsaturated
fatty acids." Journal of cardiology 67.1 (2016): 22-27.
2. Calder, Philip. "New evidence that omega-3 fatty acids have a role in primary prevention
of coronary heart disease." Journal of Public Health and Emergency 1.35 (2017).
3. Chaddha, Ashish, and Kim A. Eagle. "Omega-3 fatty acids and heart
health." Circulation 132.22 (2015): e350-e352.
4. Jain, A. P., K. K. Aggarwal, and P. Y. Zhang. "Omega-3 fatty acids and cardiovascular
disease." Eur Rev Med Pharmacol Sci 19.3 (2015): 441-5.
5. DeFilippis, Andrew Paul, Michael J. Blaha, and Terry A. Jacobson. "Omega-3 fatty acids
for cardiovascular disease prevention." Current treatment options in cardiovascular
medicine 12.4 (2010): 365-380.
6. Mozaffarian, Dariush, and Jason HY Wu. "Omega-3 fatty acids and cardiovascular
disease: effects on risk factors, molecular pathways, and clinical events." Journal of the
American College of Cardiology 58.20 (2011): 2047-2067.
7. Lavie, Carl J., et al. "Omega-3 polyunsaturated fatty acids and cardiovascular
diseases." Journal of the American College of Cardiology 54.7 (2009): 585-594.
8. Lorente-Cebrián, Silvia, et al. "Role of omega-3 fatty acids in obesity, metabolic
syndrome, and cardiovascular diseases: a review of the evidence." Journal of physiology
and biochemistry 69.3 (2013): 633-651.