ApoA1 Milano role in atherosclerosis

7/24/2019 ApoA1 Milano role in atherosclerosis

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HDLLDL


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By Padminee Krishnan

3rdyear BDS

po 1-Milano

in

atherosclerosis

ApoA1

ApoA1-Milanomutation


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Atherosclerosis is a specific form of

arteriosclerosis in which an artery wall

thickens as a result of invasion and

accumulation of foam cells.

ATHEROSCLEROSIS


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It is characterized by intimal lesions called

atheromas

An atheromatous plaque consists of a raised

lesion with a soft yellow grumous core of lipidcovered by firm white fibrous cap


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STAGES OFATHEROSCLEOSIS


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Oxidation of d and formationof foam !es

The

monocyte

engulfs the

lipid particles

Lipid laden

monocytes

FOAM CELLS

LDLFEE

!"C LS

#$O% OS%etc&

Ox-LDL

o'idation

Monocyte

Sca(enger

receptors


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Lethally Dangerous Lipoprotein versus

Highly Desirable Lipoprotein !!

HDL- transports cholesterol from peripheries to liver

anti-atherogenic

Normal value -30 to 60 mg/dl

LDL- transports cholesterol from liver to peripheral tissues

oidized " is responsible for formation of foam cells

normal value -80 t0 175mg/dl

ROLE O" hd A#D LDL


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HDL STR$CT$RE% a&oa'

ipids compleed with

proteins are lipoproteins.

#he protein part of the

lipoprotein is known as the

apolipoprotein.

#he apolipoprotein

present in HDLis ApoA1


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Endotheia dama(eDe&osition of !hoestero$&%re(uation of ABCA'Re!o(nition of u&%re(uation )y A&oA'HDL )inds to re!e&torsIn!rease in HDLtrans&orts !hoestero to i*er

Prote!ti*e roe of HDL


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$atient with

low %"&

high triglycerides

but no signs of pathology'!'!

TG


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ApoA(-)ilano is a naturally occurring mutant

variant of ApoA( of human %"

#he ApoA(-)ilano mutation was found by

*niversity of )ilan

It was discovered that this mutant variant waspresent in +., of the local population of

imone& a small village in Northern Italy

A&oA'% +iano


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#he amino acid arginine is replaced by

cysteine at position (+ in ApoA(-

)ilano

aa

aaaa

aa

Ar(inine

aa

aa Cysteine

aa

aa

Point

mutation

In ApoA1

peptie

o!

Human

HDL

1"#

1"#ApoA1-Milano

ApoA1


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#he amino acid cysteine has a sulfhydryl group

#he / of )ilano proteins occur in pairs by disulfidebridge formation

#his restricts the size and growth of %" attributing to

low %" levels.


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3,- of +iano mutation &roteins do not form

dimers and they remain monomeri!.

The free sufhydry form of the +iano

mutation is a &o/erfu anti%oxidant.

They a!t as free radi!a s!a*en(ers and

&re*ent oxidation of LDL

F$ee$ai%a

ls

mops up

unpai$eele%t$ons

P$e&ents

oxiation o!LDL ApoA1-

Milanoin

HDL

LDL


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#his in turn results in prevention of plaque formation

because only oidized " are detected and taken up by

the monocytes to form the foam cells.

#he mutated protein also targets the same receptor A01A(

2ust like the normal ApoA( proteins#his ensures that the antioidant powers concentrate where

oidation and cholesterol deposition occur thus preventing

atherosclerosis at its earliest stage!!


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Ha*in( 0no/n the ne/ a!ti*ity asso!iated

/ith the +iano &rotein that su((ests ho/ it

&rote!ts a(ainst heart disease1 this 0no/ed(e

!an )e used to e*o*e )etter thera&ies22Com)inin( the !on*entiona HDL thera&y /ith

the +iano mutation &rotein /i &ro*ide a

more e!ient treatment22

"$T$RE SCOPE


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Study of iterature says that the !arriers of

this +iano &rotein are free from

!ardio*as!uar disorders for more than4,years no/ after its dis!o*ery.

It has stood the test of time1 &romisin(

ne/ thera&ies to !om)at the /ord5s

eadin( !ause of death22

CO#CL$SIO#


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THA'( )O*

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ApoA1 Milano role in atherosclerosis