Review Article

Adiponectin and Atherosclerosis

Yusdeny Lanasakti Iswanto Pratanu

Department of Cardiology Dr Soetomo Teaching HospitalAirlangga University School of Medicine SURABAYA

Adiponectin & Atherosclerosis

Introducti on
The worldwide epidemic of obesity has occurred prevalence of cardiovascular disease (CVD) Adipose tissue dysfunction in obesity associated with Coronary Heart Disease (CHD) Adipose release several adipokines some beneficial and some deleterious on the cardiovascular Adiponectin adipokines which have a protective effect of CV widely studied as a therapeutic target in atherosclerosis

Adiponectin & Atherosclerosis

Adipose Tissue Depots

Ouchi,201 1

Adipokines
Heart Vascular tissue Skeletal muscle Liver

BP,Fibrinolisis,anti-atherogenesis ApN Apelin

Cardiovascular function

Insulin sensitivity
ApN Leptin Apelin

Kidney PAI-1 AGT

TNF- RBP-4? IL-6? Pancreas

Adipocytes

Visfatin

Leptin ApN Apelin TNF-

Insulin secretion Expanded Fat mass

ApN TNF- MCP-1 IL-6

Stimulation Inhibition

E. Maury, 2010

Inflamati on
4

Adipokines within Adipose Tissue.

LEPTIN ADIPONECTIN IL-6 IL-18 RESISTIN TNF- CCL2 CCL2CXCL5 Visfatin ANGPTL 2 PAI-1 Ouchi, 2011; Smith, 2011 Omentin

APELIN

Adiponectin

ADIPONECT IN Discovered in 1990

HMW

by 4 different research Acrp30, AdipoQ, apM1, GBP28

The largest amount adipokin in the bloodThe gen located on chromosome 3q27

MMW

Form oligomeric multimer in circulationLMW,MMW & HMW

LMW

In Japanese non obese subject adipoQ levels 3-30 g/dl and decrease 50% in obesity
6

AdipoQ & CHD

ADIPOnectin and CHD

Hipoadiponektin associated with the prevalence of CHD

Adiponectin levels < 4 g/dl has 2-fold risk of CHD

Adiponectin level correlated with the severity of coronary lession

Adiponectin has protective effect against pro inflammatory mediators in atherosclerosis

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Pathophysiology of atherosclerosis

LDL

ROS

DL oxL
-1 LOX

endothel
Intima

Macrophage

DC
T limphocyte

Media

SMC

Atherosclerosis
Pathophysiogy
Bone marrow
Monocyte
M-1 VCA ICA M-1

DL oxL
-1 LOX

endothel
DC

Intima
di ffe

i nt e r

M CP

n io t a

-1

TNF- , IL-6, IL-8

Macrophage

C M-

SF

T limphocyte

Media SMC

Atherosclerosis
Pathophysiogy

-1 M-1 ICAM A VC

-1 LOX

Intima
Macrophage

PD GF TN F -

Media

Mi gr

ati o

SR

Foam cell

AdipoQ & CHD

ADIPOnectin and CHD

Inhibitors of Adiponectin Expression
Inhibitors TNF- inhibits adiponectin
production in adipose tissue

References
Ouchi,1999 Fasshauer, 2003

IL-6

inhibits adiponectin adiponectin gene expression and secretion in 3T3-L1 adipocytes

CRP

inhibits adiponectin mRNA levels in humans adipose tissues

Ouchi, 2003 Motoshima, 2002; Fasshauer, 2002

Insulin

supresses gene expression of adiponectin in adipocytes

Glucocorticoids

supress gene expression of adiponectin in adipocytes

Fasshauer, 2002

Beta-adrenergic agonist
inhibits gene expression of adiponectin

Fasshauer, 2001

Hydrogen peroxide and nicotine reduce expression and

secretion of adiponectin

Fasshauer, 2002

Han, 2007 11

Therapeutic Intervention on Raising AdipoQ Level

Life Style Modifications
Weight loss restores adiponectin levels Combined diet control and physical exercise increases plasma levels of adiponectin Smoking habit decreases plasma adiponectin concentration Increasing activity of the sympathetic nervous system decrease plasma level of adiponectin

References
Hotta,2000; Kobayashi,2004 Esposito,2003; Monzillo, 2003 Miyazaki,2003; Iwashima,2005 Fasshauer, 2001

Renin-Angiotensin System Blocking Agent Koh, 2005 Termocapril and Ramipril increase adiponectin levels Koh,2004; Koh,2006; Losartan and Candersartan increase adiponectin levels PPAR Agonist Chinetti , 2004 PPAR Agonist induces AdipoR2 on human primary macrophage Chinetti , 2004; Koh,2005; Fenofibrate increase adiponectin levels
Koh,2006

PPAR Agonist Thiazolidinediones induces expression and secretion of adiponectin Maeda,2001

in humans and rodent in vivo and in vitro Thiazolidinediones increase adiponectin levels in diabetic, lean Yu, 2002 control, and obese control subjects

Hypoglicemic Drugs
Increase plasma adiponectin levels in elderly patients Tsunekawa, 2003 with type 2 diabetes Metformin does not alter plasma adiponectin levels in obese patients Philips, 2003 with type 2 diabetes

Glimepiride

Statin Simvastatin, atorvastatin, and rosuvastatin do not change plasma Koh, 2004; Koh, 2005; Avest,
levels of adiponectin 2005

New Beta-Blockers Nebivolol increase plasma adiponectin levels in hypertensive patients

Celik, 2006 Han, 2007

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AdipoQ & Atherosclerosis

Barseghian, 2011
13

Role of Adiponectin in Inhibit Atherosclerosis

Adipose Tissue Vasculature
Monocyte Adhesion NO production Endothelial

Adiponecti n

Apoptosis endoth Foam cell formation Inflammation Efflux chol.

TNF- CRP

Inflammation

Macrophage Migration, Proliferation

SMC

Atherosclerosis

Summary
Adipose tissue dysfunction obesity associated with CHD in

Adiponectin is adipokine which has the effect of anti-atherosclerotic Adiponectin has been the target of future research to fight against atherosclerotic Optimism arising to recombinant adiponectin as a treatment and prevention of CVD

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Human Adipocyte
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