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Calvo et al. Omega-3 fatty acids in cardiovascular health

INTRODUCTION chain are called PUFAs, which are classified in 2 main
subgroups: n-6 long chain PUFAs (n-6 LC-PUFAs)
Cardiovascular disease (CVD) represents an ongoing and n-3 long chain PUFAs (n-3 LC-PUFAs), which
global epidemic. In 2014, 27.6 million people were are commonly referred to as omega-6 and omega-3
diagnosed with CVD worldwide, and by 2030, it may PUFAs, respectively. [17] The former are LA derivatives
[1]
be responsible for up to 23.5 million deaths yearly. [2] with 2 double bonds, which are located 6 carbons away
These trends are common in all westernized countries, from the methyl end (18:2Ω6); whereas n-3 LC-PUFAs
including Latin America. In Venezuela, 29.47% of derive from ALA and have 3 double bonds, with the first
all mortality was attributed to CVD in 2012. Given one being in the third carbon of the chain (18:3Ω3) [18,19]
[3]
the heavy burden CVD represents for public health [Figure 1].
systems, prevention has become a key component
in clinical practice and research, oriented to the Metabolism and general biologic functions of
identification and management of several risk factors, essential PUFAs
both modifiable and non-modifiable. Regarding The metabolism of both types of PUFAs ends in
[4]
modifiable risk factors, westernized dietary patterns, the formation of eicosanoids, which are biologically
notable for their high intake of dairy products, refined active compounds including prostaglandins (PGs),
carbohydrates and saturated fats, have been strongly thromboxanes (TXs) and leukotrienes (LTs). [18]
linked with the development of not only CVD, but As shown in Figure 1, arachidonic acid (AA) is
also hypertension (HTN), obesity and type 2 diabetes synthetized from LA (n-6), and is converted by the
mellitus. [5-7] action of cyclooxygenase (COX) and lipoxygenase
(LOX) into 2-series PGs and TXs and 4-series LTs and
[8]
In 1980, Bang et al. studied the diet of the Eskimo lipoxines. Although these mediators intervene in both
population of Greenland, characterized by high intake the establishment and resolution of the inflammatory
of foods rich in long chain polyunsaturated fatty acids response, their net effect is predominantly pro-
(LC-PUFAs), and paradoxically found a low incidence inflammatory. [19,20] In contrast, ALA (n-3) is a precursor
of CVD in these individuals. From these pioneer of eicosapentaenoic acid (EPA) and docosahexaenoic
[9]
studies, different epidemiological and interventional acid (DHA), from which 3-series PGs and TXs,
investigations have backed the cardioprotective role of as well as 5-series LTs, lipoxins, resolvins and
n-3 LC-PUFAs. [10,11] neuroprotectins are derived. These compounds have
chiefly anti-inflammatory effects, [17] which is why
Although many beneficial CV effects have been current nutritional guidelines are oriented towards an
ascribed to PUFAs, including hypolipidemic, increase in n-3 PUFAs intake. [21-24] Furthermore, the
antithrombotic, antihypertensive and antiarrhythmic products of both series mediate the regulation of other
properties, [12,13] the underlying molecular mechanisms physiological processes, such as the maintenance
remain to be elucidated. This review aims to offer an of cell membrane architecture, especially through
integrated state-of-the-art vision into the structure of their arrangement in lipid rafts, [25,26] and play a role
PUFAs and their functions in the CV system. in hemostasis and vasoconstriction, which are further
explained ahead. [18,27]
GENERAL OVERVIEW OF PUFAS
Role of PUFAs in cell membrane maintenance
Structure and classification The long hydrocarbon chains and double bonds in EPA
Fatty acids are molecules consisting of a long linear and DHA exert modifications on the cell membrane
hydrocarbon chain that generally contains a pair due to their length and degree of unsaturation.
[28]
number of carbon atoms between 12 and 24, with These molecules have been demonstrated to
a carboxyl (-COOH) group in one end and a methyl increase membrane fluidity and modify the size and
(-CH3) group in the other. [14] They are termed saturated distribution of lipid rafts in aortic endothelial cells
fatty acids when only simple bonds exist between the and rat lymphocyte cultures. [29,30] Lipid rafts are
carbon atoms, while those that have one or more dynamic membrane microdomains containing sterols,
double bonds are known as unsaturated fatty acids. [15] enriched sphingolipids and specific binding proteins,
The latter include widely recognized nutritionally which attain a metastable resting state through a
essential molecules for humans and other animal constellation of lipid-lipid, protein-lipid and protein-
species, including linoleic acid (LA) and α-linoleic acid protein bonds. [31] Incorporation of n-3 PUFAs in lipid
(ALA). [16] rafts results in decreased cholesterol and sphingolipids
in these microdomains. [32] This has been confirmed by
Fatty acids with more than one double bond in their systematic studies in membrane models that suggest
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