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Atherosclerosis

The word Atherosclerosis comes from the ancient Greeks where "sclerosis means
hardening and athere is gruel oraccumulationoflipid.
Atherosclerosis,orhardeningofthe
arteries, is a condition in which plaque builds up inside the arteries. Plaque is made of
cholesterol, fatty substances, cellular waste products, calcium and fibrin (a clotting material
in the blood).
It is the most important source of morbidity andmortalityintheworld,andis
detected by the accumulation of lipids deposits (mainly cholesterol) in macrophages located
not only in large but also in medium sized arteries. The physiopathological process is
characterized by the aggregation of cholesterol, infiltration of macrophages and the
proliferation of smooth muscle cells (SMCs) as accumulation of connective tissues and
thrombuscreation.

Heart
The heart is a muscular organ about the size of a fist,locatedjustbehindandslightly
left ofthebreastbone.Theheartpumpsbloodthroughthenetworkofarteriesandveinscalled
thecardiovascularsystem.
Thehearthasfourchambers:

Therightatriumreceivesbloodfromtheveinsandpumpsittotherightventricle.

The right ventricle receives blood from the right atrium and pumps it to the lungs,
whereitisloadedwithoxygen.

The left atrium receives oxygenated blood from the lungs and pumps it to the left
ventricle.

The left ventricle (the strongest chamber) pumps oxygenrich blood to the rest ofthe
body.Theleftventriclesvigorouscontractionscreateourbloodpressure.
The coronary arteries run along the surface of the heart and provide oxygenrich

blood to the heart muscle. A web of nerve tissue also runs through the heart, conductingthe
complex signals that govern contraction and relaxation. Surrounding the heart isasaccalled
thepericardium.

Aorta:

Theaortais the main


artery
in the
human body
, originating from the
left ventricle
of
the
heart
and extending down to the
abdomen
, where it
splits
into two smaller arteries
(the
common iliac arteries
). The aorta distributes
oxygenated
blood to all parts of the body
throughthe
systemiccirculation
(Anthea
etal.,
1995).

The aorta supplies all of the systemic circulation, which means that the entire body,
except for the
respiratory zone of the lung
, receives its blood from the aorta. Broadly
speaking, branches from the ascending aorta supply the heart branches from the aortic arch
supply the head,neckandarmsbranchesfromthethoracicdescendingaortasupplythechest
(excluding the heart and the respiratory zone of the lung) and branches from the abdominal
aortasupplythe

abdomen
.Thepelvisandlegsgettheirbloodfromthecommoniliacarteries.

Commonsymptomsinclude:

chestpainorangina.

paininyourleg,arm,andanywhereelsethathasablockedartery.

shortnessofbreath.

fatigue.

confusion,whichoccursiftheblockageaffectscirculationtoyourbrain.

muscleweaknessinyourlegsfromlackofcirculation.
RiskFactors:
Modifiable:
1.Hyperlipidemia
2.Hypertension
3.Cigartte
4.smoking
5.diabetesmellitus
NonModifiable
1.age
2.gender
3.genetic
4.prediposition
5.elevatedLdlCholestrol
LDLOxidation
Oxidation of lowdensity lipoprotein (LDL) plays an important role in the
pathogenesis of atherosclerosis. LDL can be oxidized by metal ions, lipoxygenases,
myeloperoxidase, and reactive nitrogen species.OxidationofLDLbymetalions(e.g.,Cu21)
occurs in three phases: an initial lag phase (consumption of endogenous antioxidants), a
propagation phase (rapid oxidation of unsaturated fatty acids to lipid hydroperoxides), and a
decomposition phase (hydroperoxides are converted to reactive aldehydes, e.g.,
malondialdehyde,4hydroxynonenal)(Gotta
etal
.,1986).


Interaction of these aldehydes with positively charged amino groups of lysine
residues renders the LDL more negatively charged, resulting in decreased affinity for the
LDLreceptorandincreasedaffinityforscavengerreceptors.

Lipooxygenase
15Lipoxygenase, produced by endothelial cells and monocytes/macrophages,
converts polyunsaturated fatty acids into lipid hydroperoxides and thereby oxidizes LDL.
Overexpression of 15lipoxygenase in vascular endothelium accelerates earlyatherosclerosis
in LDL receptordeficient. The lipoxygenase metabolite of arachidonic acid, results in
enhanced adhesion of monocytes to endothelium, a key earlyeventinatherogenesis(Metens
etal.,
2001)
Myeloperoxidase
Activated phagocytes secrete myeloperoxidase that generates reactive species
including hypochlorous acid (HOCl), chloramines, tyrosyl radicals, and nitrogen dioxide

(NO2). These reactive species oxidize antioxidants, lipids, and protein of LDL (10) (Fig.1).
Reactive nitrogen species generated by the myeloperoxidase H2O2NO2 system of
monocytes convert LDL into an atherogenic form that is avidly taken up and degraded by
macrophages,leadingtofoamcellformation(Podrezetal.,1999).

HDL
HDLassociated enzyme, paraoxonase (PON), was capable of preventing the
accumulation of lipid hydroperoxides in LDL. HDL from normal subjects prevented
cellmediated oxidationofLDLandpreventedtheinductionofMCP1byLDL
(Navab
etal.,
2008). HDL cholesterol levels are inversely related to risk of coronary artery disease. HDL
prevents atherosclerosis by reverting the stimulatory effect of oxidized LDL on monocyte
infiltration. The HDLassociated Enzyme paraoxonase inhibits the oxidation of LDL.
PAFacetyl hydrolase, which circulates in association with HDL and is produced in the
arterial wall by macrophages, degrades bioactive oxidized phospholipids. Both enzymes
activelyprotectagainstatherosclerosis(Mertens
etal.,
2001).
Paraoxonase
Paraoxonases are a group of enzymes involved in the hydrolysis of organophosphates and
lactones
.(Laetal
.
,1991).Thereare3knowngenotypicformsofparaoxonases.Theyarecoded
for by the PON set of genes PON1, PON2 and PON3 located on the long arm of
chromosome7

inhumans(Grossetal.,2004).
PON1 is synthesized in the liver and transported along with HDL intheplasma.Itfunctionsas
an a
ntioxidant
it prevents the oxidation of LDL
. Its serum concentration is influenced by
inflammatorychangesandthelevelsofserumoxidisedLDL(Liangetal.,2003)
PON2 is a ubiquitously expressed intracellular protein that can protect cells against oxidative
damage
(
wadleighetal.,2001)
PON3 is similar to PON1 in activity but differs from it in substrate specificity. Serum PON3
activity is 100 times lower than PON1. Additionally, it is not regulated by inflammation and
levelsofoxidisedlipids.(wadleighetal.,2001)

PON1
PON1 was shown to protectbothLDLandHDLagainstlipidperoxidation.Inhibition
of HDL oxidation by PON1 preserves the antiatherogenic effects of HDL in reverse
cholesterol transport. PON1 can hydrolyze specific oxidized cholesteryl esters, as well as
specific oxidized phospholipids in oxidized lipoproteins Oxidized lipids inoxidizedLDLor
in oxidized HDL were shown to inactivate PON1, and the PON1Q isoform was found to be
less inactivatedthanthePON1RisoformAntioxidantssuchastheflavonoidsglabridin(from
licorice) or quercetin (from red wine), when present during LDL oxidation, together with
PON1 significantly reduced the content of lipoproteinassociated lipid peroxides and
preserved PON1 activities, including its ability to hydrolyze OxLDL cholesteryl linoleate
hydroperoxides.HDLassociated PON1 was recently shown to protect macrophages against
oxidativestressbyhydrolyzingoxidizedlipids,byinhibitingcellmediatedoxidationofLDL,
andbyattenuatingtheuptakeofoxidizedLDL(Aviram
etal
.,2004).
PON2
AsthesecondmemberofthePONgenefamily,PON2geneshares79%90%identity
with PON1 . PON2 is thought to be able to lower intracellular oxidative stress and prevent
cellular oxidation of LDL, although its aromatic ester and PON hydrolyzing activities are
lower than those of PON1. Cells over expressing PON2 are less able to oxidize LDL and
showsignificantlylessintracellularoxidativestresswhenexposedtoeitherH2O2oroxidized
phospholipids (245), suggesting that PON2 plays a protective role in atherosclerosis. PON2
has been found to be able to prevent mitochondrial superoxide formation and apoptosis of
cells(She
etal.,
2007).

PON3
PON3 is an 40kDa protein primarily synthesizedintheliverandisassociatedwith
HDLfractionsofhumanplasma.PON3notonlypreventstheformationofMMLDLbutalso
inhibits MMLDLinduced monocyte chemotactic activity. Our data suggest that PON3 is
similar to PON1 in its association with HDL and the prevention of MMLDL formation or
the inactivation of MMLDL. However, unlike PON1, PON3 expression is not affected in
HepG2 cells by oxidized phospholipids or in the livers of mice by a highfat diet (Reddy
et
al
.,2001).

Blacktea
Black teais a type of
tea
that is more
oxidized
than
oolong
,
green
and
white
teas.
Black tea is generally stronger in flavor than the less oxidized teas. All four types are made
from leaves of
the
shrub
(or small tree)
Camellia sinensis
. Two principal varieties of the
species are used the smallleaved Chinese variety plant (
C. sinensis
subsp.
sinensis
), used
for most other types of teas, and the largeleaved Assamese plant (
C.
sinensis
subsp.
assamica
), which was traditionally mainly used for black tea, although in
recentyearssomegreenandwhitehavebeenproduced.
BlackTeaandCardiovasculardiseases
Among the most intensively studied of general human disorders possibly affected by
dietary flavonoids, preliminary
cardiovascular disease
research has revealed the following
mechanismsunderinvestigationinpatientsornormalsubjects.

inhibit
coagulation
,
thrombus
formationor
plateletaggregation

reduceriskof
atherosclerosis

reduce
arterialbloodpressure
andriskof
hypertension

reduce
oxidativestress
andrelated
signalingpathways
in
bloodvessel
cells

modifyvascular
inflammatory
mechanisms

improve
endothelial
and
capillary
function

modify
bloodlipid
levels

regulate
carbohydrate
and
glucosemetabolism

modifymechanismsof
aging

Listed on the
clinical trial
registry of the US
National Institutes of Health
(November 2013)
are 36 human studies completed or underway to study the dietary effects ofplantflavonoids
oncardiovasculardiseases.
BlackteaandAntioxidant
Research

at

the
Linus

Pauling Institute
and the
European Food Safety

Authority
shows that flavonoids are poorly absorbed in the human body(lessthan5%),with
mostofwhatisabsorbedbeingquicklymetabolizedandexcreted.Thesefindingssuggestthat
flavonoids have negligible systemic antioxidant activity, and that the increase in antioxidant
capacity of blood seen after consumption of flavonoidrich foods is not caused directly by
flavonoids,

but is due to production of


uric acid
resulting from flavonoid

depolymerization
and
excretion
.