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Review ArticleReview Article

Adiponectin andAtherosclerosis

Yusdeny LanasaktiIswanto Pratanu

Department of CardiologyDr Soetomo Teaching Hospital-Airlangga University School of

Medicine

SURABAYA


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Adipose release several adipokines

some beneficial and somedeleterious on the cardiovascular

Adipose tissue dysfunction inobesity associated with CoronaryHeart Disease (CHD)

The worldwide epidemic of obesityhas occurred prevalence ofcardiovascular disease (CVD)

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Adiponectin & AtherosclerosisAdiponectin & Atherosclerosis

Introduction

Adiponectin adipokines whichhave a protective effect of CV widely studied as a therapeutic

target in atherosclerosis


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3

Adiponectin & AtherosclerosisAdiponectin & Atherosclerosis

Adipose Tissue

Depots

Ouchi,2011


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4

AdipokinesAdipokines

E. Maury, 2010

Kidney

HeartVascular tissue Skeletal

muscle

Liver

Stimulation

Inhibition

Cardiovascular function Insulin sensitivity

Insulinsecretion

Pancreas

BP,Fibrinolisis,anti-atherogenesis

Expanded

Fat mass

ApNLeptin

Apelin

TNF-

VisfatinAdipocytes

PAI-1AGT

ApN

Apelin

Apelin

ApN

Leptin

ApN

TNF-

RBP-4?IL-6?

TNF-

IL-6

MCP-1

Inflamati

on


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LEPTIN

ADIPONECTIN

IL-6

ANGPTL2

CCL2

Omentin

Adipokines within Adipose Tissue.

TNF-

IL-18

PAI-1

Ouchi, 2011; Smith, 2011

CCL2CXCL5

RESISTIN

APELIN

Visfatin


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Form oligomeric multimer incirculationLMW,MMW & HMW

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AdiponectinAdiponectin

ADIPONECT

IN

HMW

MMW

LMW

Discovered in 1990 by 4 differentresearch Acrp30, AdipoQ, apM1,GBP28

The largest amount adipokin in the

bloodThe gen located onchromosome 3q27

In Japanese non obese subjectadipoQ levels 3-30 g/dl anddecrease 50% in obesity


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AdipoQ & CHDAdipoQ & CHD

ADIPOnectin and CHD

Hipoadiponektin associated withthe prevalence of CHD

Adiponectin levels < 4 g/dl has2-fold risk of CHD

Adiponectin level correlated withthe severity of coronary lession

Adiponectin has protective effectagainst pro inflammatorymediators in atherosclerosis


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Pathophysiology of atherosclerosis

LDL ROS

oxLDL

LOX-1

endothel

Intima

Media T limphocyte

Macrophage

SMC

DC


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oxLDL

LOX-1

endothel

Intima

Media

T limphocyte

Macrophage

SMC

DC

Pathophysiogy

MCP-1

Bone

marrow

Monocyte

VCAM

-1 ICAM-1

TNF-

, IL-6, IL-8 M-CSF

diffe

rentia

tion

AtherosclerosisAtherosclerosis


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LOX-1

Intima

Media

Macrophage

M

igrati

onSR

Pathophysiogy

Foamcell

VCAM

-1ICA

M-1


PDGF

TNF

-


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AdipoQ & CHDAdipoQ & CHD

ADIPOnectin and CHD

Inhibitors of Adiponectin ExpressionInhibitors References

TNF-inhibits adiponectinproduction in adipose tissue

Ouchi,1999

IL-6 inhibits adiponectinadiponectin gene expression and

secretion in 3T3-L1 adipocytes

Fasshauer, 2003

CRPinhibits adiponectin mRNAlevels in humans adipose tissues

Ouchi, 2003

Insulin supresses geneexpression of adiponectin inadipocytes

Motoshima, 2002; Fasshauer, 2002

Glucocorticoids supress gene

expression of adiponectin inadipocytes

Fasshauer, 2002

Beta-adrenergic agonistinhibits gene expression ofadiponectin

Fasshauer, 2001

Hydrogen peroxide andnicotine reduce expression andsecretion of adiponectin

Fasshauer, 2002

Han, 2007


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Therapeutic Intervention on Raising AdipoQ LevelTherapeutic Intervention on Raising AdipoQ Level

Life Style Modifications ReferencesWeight loss restores adiponectin levels Hotta,2000; Kobayashi,2004Combined diet control and physical exercise increases plasma levels of

adiponectin

Esposito,2003; Monzillo, 2003

Smoking habit decreases plasma adiponectin concentration Miyazaki,2003; Iwashima,2005Increasing activity of the sympathetic nervous system decrease plasmalevel of adiponectin

Fasshauer, 2001

Renin-Angiotensin System Blocking AgentTermocapril and Ramipril increase adiponectin levels Koh, 2005

LosartanandCandersartan increase adiponectin levels Koh,2004; Koh,2006;

PPAR Agonist

PPAR Agonist induces AdipoR2 on human primary macrophage Chinetti , 2004

Fenofibrate increase adiponectin levels Chinetti , 2004; Koh,2005;Koh,2006

PPAR AgonistThiazolidinediones induces expression and secretion of adiponectinin humans and rodent in vivo and in vitro

Maeda,2001

Thiazolidinediones increase adiponectin levels in diabetic, leancontrol, and obese control subjects

Yu, 2002

Hypoglicemic DrugsGlimepiride Increase plasma adiponectin levels in elderly patientswith type 2 diabetes

Tsunekawa, 2003

Metformin does notalter plasma adiponectin levels in obese patientswith type 2 diabetes

Philips, 2003

StatinSimvastatin, atorvastatin, and rosuvastatin do not change plasmalevels of adiponectin

Koh, 2004; Koh, 2005; Avest,2005

New Beta-BlockersNebivolol increase plasma adiponectin levels in hypertensive patients Celik, 2006Han, 2007


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AdipoQ & AtherosclerosisAdipoQ & Atherosclerosis

Barseghian, 2011


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Adiponectin

InflammationTNF- CRP

Adipose Tissue

SMC

Macrophage

Endothelial

Vasculature

NO production

Monocyte Adhesion

Foam cell formationInflammation

Efflux chol.

Migration, Proliferation

Apoptosis endoth

Role of Adiponectin in Inhibit

Atherosclerosis


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Summary

Adipose tissue dysfunction inobesity associated with CHD

Adiponectin is adipokine which hasthe effect of anti-atherosclerotic

Adiponectin has been the target offuture research to fight againstatherosclerotic

Optimism arising to recombinantadiponectin as a treatment andprevention of CVD


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HumanAdipocyte

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