Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Look up keyword
Like this
19Activity
0 of .
Results for:
No results containing your search query
P. 1
American Heart Journal 2007. Human epicardial adipose tissue: A review. By Harold Sacks.

American Heart Journal 2007. Human epicardial adipose tissue: A review. By Harold Sacks.

Ratings:

5.0

(1)
|Views: 2,185|Likes:
Published by David O Sacks
Human epicardial adipose tissue: A review.
Human epicardial adipose tissue: A review.

More info:

Categories:Types, Research, Science
Published by: David O Sacks on Jun 01, 2007
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

01/01/2013

pdf

text

original

 
Humanepicardialadiposetissue:Areview
HaroldS.Sacks,MD,aandJohnN.Fain,PhDb
Memphis,TN
Wediscusstheanatomy,physiology,andpathophysiologyofepicardialadiposetissueanditsrelationshiptocoronaryatherosclerosis.Epicardialfatstorestriglyceridetosupplyfreefattyacidsformyocardialenergyproductionandproducesadipokines.Itsharesacommonembryologicaloriginwithmesentericandomentalfat.Likevisceralabdominalfat,epicardialfatthickness,measuredbyechocardiography,isincreasedinobesity.Epicardialfatcouldinfluencecoronaryatherogenesisandmyocardialfunctionbecausethereisnofibrousfasciallayertoimpedediffusionoffreefattyacidsandadipokinesbetweenitandtheunderlyingvesselwallaswellasthemyocardium.Segmentsofcoronaryarterieslackingepicardialfatorseparatedfromitbyabridgeofmyocardialtissueareprotectedagainstthedevelopmentofatherosclerosisinthosesegments.However,whenepicardialfatistotallyabsentincongenitalgeneralizedlipodystrophy,coronaryatherosclerosiscanstilloccur.Macrophagesaremorenumerousanddenselypackedintheperiadventitialfatofhumanatheroscleroticcoronaryarterieswithlipidcoresthaninthatoffibrocalcificornonatheroscleroticcoronaryarteries.Inobesepatientswithmultiplecardiovascularriskfactors,epicardialfataroundatheromatouscoronariessecretesseveralproinflammatorycytokinesandisinfiltratedbymacrophages,lymphocytes,andbasophils.Epicardialadipokineexpressioninobesitywithoutcoronaryatherosclerosishasnotbeendetermined.Innonobesepatients,epicardialfataroundatheromatouscoronaryarteriesexpressesproinflammatorycytokinesbutproduceseitherlessadiponectin,avasoprotectiveadipokine,thanfataroundnonatheromatouscoronariesorasimilaramountcomparedwiththoracicsubcutaneousfat.Furtherstudiesshouldbedonetotestthehypothesisthatadipokinesproducedbyandreleasedfromhumanepicardialadiposetissuemightcontributelocallytothepathogenesisofcoronaryatherosclerosis.(AmHeartJ2007;153:907-17.)Humanepicardialadiposetissue(EA1)isavisceralthoracicfatbecauseofitsappositiontotheheart,toahollowmuscularorgan,ortotheviscus.IthasnotbeenstudiedasthoroughlyIasvisceralabdominaladiposetissue0'A1)andsubcutaneousabdominaladiposetissue(SCA1).2LikeotherwhiteadiposetissueIOci,3-6EATmightfunctionasalipid-storingdepot,asanendocrineorgansecretinghormones,andasaninflammatorytissuesecretingcytokinesandchemokines.Underthesecon-ditions,itsproximitytotheadventitiaofthecoronaryarteries(Figure1)andtheunderlyingmyocardiumsuggeststhepossibilitythatitcouldplayaroleinthepathogenesisofcoronaryatherosclerosis(CAD),itselfachronicinflammatorydisease,Iandcardiomyopathy(CMO).Theobesityepidemicinchildren7andadultshasdrawnattentiontoVATandthemetabolicsyndromeRas
From
the"Division
of
EndocrinologyandMetabolism.University
ofTennessee,
and
BaptistHospitalHeartInsritute,Memphis,TN,andbDepartment
of
MolecularSciences,College
of
Medicine,University
ofTennessee
HealthScienceCenter,Memphis.TN.Disclosure:Harold
S.
Socks
isa
member
of
theSpeakersBureauandhasreceivedhonoraria
from
TakedaPharmaceuticalsandMerckPharmaceuticals.SubmiffedOctober
19,
2006;acceptedMarch
13,
2007.Reprintrequests:Harold
S.
Socks,MD,6027WalnutGroveRoad,suite307,Memphis,
TN
38120.E-mail:hsacks@hotmail.com0002.B703/$
.
seefrontmaffer
<!::>
007,Mosby,Inc.
All
rightsreserved.doi:10.
10
16/j.ahj-2007.03_019
riskfactorsforcardiovasculardisease(CVD)andtype2diabetesmellitus(DM)9.1OandposeswhetherobesitypersecouldaffectEATanditsadipokinecontent.WediscusstheanatomyandphysiologyofhumanEAT,thepathophysiologyofwhiteadiposetissueinobesitycomparedtothenonobesestate,thepatho-physiologyofEAT,andtheputativeroleofEATinthepathogenesisofCADandCMO.
AnatomyandphysiologyofEAT
Theepicardiumorviscerallayerofthepericardiumisapopulationofmesothelialcellsthatmigrateontothesurfaceoftheheartfromtheareaoftheseptumtransversum(theembryologicalsourceofthedia-phragm).Epicardial,mesenteric,andomentalfatallsharethesameoriginfromthesplanchnopleuricmesoderm
associatedwiththegut.
11
Inthenormaladult,epicardial
fatisconcentratedintheatrioventricular(AV)andinterventricular(IV)groovesandalongthemajorbranchesofthecoronaryarteries,and,toalesserextent,aroundtheatria,overthefreewalloftherightventricle(RV)andovertheapexoftheleftventricle(LV).12,13Pericardialfat(pericardialadiposetissue[PAT])isdefinedasepicardialfatinallthesepossiblelocationsplusparacardialfat.14Paracardialfatissituatedontheexternalsurfaceoftheparietalpericardiumwithinthemediasti-numandhasalternativelybeentermedmediastinalfat.15
 
908
Sacks
andFain
Figure
1
Histologyoftherightcoronaryarteryandperiadventitialepicardialfat.Thishighpower(x100magni~cation)hematoxylinandeosinstainofatransverseautopsysectionoftherightcoronaryarteryfromapatientwithhypertensiveheartdiseaseshowsthelayersofthearterywall,thetissuestructuresinepicardialfat,andtheclosecontactofepicardialadipocyteswiththeadventitia.
Paracardialfatoriginatesfromtheprimitivethoracicmesenchyme,whichsplitstoformtheparietal(fibrous)pericardiumandtheouterthoracicwall.16Epicardialadiposetissueissuppliedbybranchesofthecoronaryarteries,whereasparacardialfatissuppliedfromdifferentsourcesincludingthepericardiacophrenicartery,abranchoftheinternalmammary.17Lipolysisandlipogenesishavenotbeenmeasureddirectlyinhumanepicardialfat.Basedonapproximately2-foldhigherratesoflipolysisandlipogenesisinguinea-pigepicardialfatthanotherfatdepots,Marchingtoneta118,19proposedthatEATservestocaptureandstoreintravascularfreefattyacid(FFA)toprotectcardiomyo-cytesfromexposuretoexcessivecoronaryarterialFFAconcentrationsduringincreasedenergyintakeand,atothertimes,toreleaseFFAasanimmediateATPsourceforthemyocardiumduringperiodsofneed.Epicardialfatandthemyocardiumarecontiguous.IslandsofmatureadipocytesaremorefrequentwithinthesubepicardialmyocardiumoftheRVthantheLV13andmayactasmorereadilyavailable,directsourcesofFFAforcardiomyo-cytes.Thethicknessofthewalloftherightatriumisabout2mm;theleftatrium,3to5mm;theRV,3to5mm;andtheLV,13to15mm.20Possibly,FFAscoulddiffusebidirectionallyininterstitialfluidacrossconcentrationgradientsfromepicardialfatintotheatrialandRVwallswhereEATpredominatesandviceversa,butthisprocessintheLVwallcanbequestionedbecausethediffusiondistanceismuchlonger.
AmericanHearlJournaiJune
2007
Innormalhumans,systemicfatstoresaretheprincipal
')1
sourceofFFAsfortheheart.-ThemyocardiumextractsandmetabolizesFFAsfromcoronaryarterialblood.Freefattyacidkineticstudiesshowthatundernormalbasalconditions,endogenousFFAsarereleasedintothecoronaryveinsandthenintothecoronaryvenoussinus.21.22ThesourceforthisFFAreleaseisthoughttobeEATlipolysis,22sinceotherpossibilitiessuchashydrolysisofintracardiomyocytetriglycerideorhydrolysisofcircu-latingvery-Iow-density-lipoprotein-triglycerideincoro-naryblood21seemunlikely.ThereasonforFFAeffluxintocoronaryvenousbloodisunclear.Itmightrepresentan"overflow"ofFFAsnotusedbythemyocardium.Alternatively,itmightbeadirectsourceofFFAsforthepulmonaryarterialcirculation,sincevasoactiveprosta-noidsaregeneratedbythepulmonaryarterialendothe-liumfromFFAprecursors.23ThefactthatcoronarysinusFFAappearanceaccountsforaminorfractionofsystemicFFAflUX22upportsthehypothesisthatEATfunctionsasalocalmyocardium-specifictriglyceridedepot.Epicardialadiposetissuemightsecretevasoactiveproductsthatregulatecoronaryarterialtone.Forexample,adipocyte-derivedrelaxingfactor,aproteinrecentlyisolatedfromnormalrodentaorticandmesentericarterialperiadven-titialfat,24stimulatesarterialvasodilationindependentlyofnitricoxidebydiffusingintothemediaofthecoronarywall,normally0.55to1.0mmthick25Itisdifferentfromleptin24andadiponectin.26
QuantitationofEAT
Autopsy
Corradietal27dissectedepicardialfatfromtheunderlyingmyocardiuminaseriesof117patientsandfoundthatitaccountedforapproximately15%(mean,54I23g[ISDJ)ofanormalheartweight(365I49g).TheyalsofoundadirectcorrelationbetweenLVandRVmassandcorrespondingepicardialfatmass.Inalaterstudy,thesameauthorsconfirmedthedirectcorrelation
(r
=
0.755,
P
=
.01)betweenEATmassandmyocardialventricularmassmeasuredbyechocardiographyin60subjectswithnoknowncardiacdisease.28Inanunselectedgroupof200patientsdyingfromavarietyofdiseasesincludingcarcinomaandarteriosclerosisstudiedbySchjebal,29epicardialfatthicknessovertheRVwallvariedfromzeroalongthefat.freediaphragmaticregionto13.6mmalongthesharpventrolateraledgeclosetothebase,themaximalpointofthickness.Inthatreport,EATthicknesscorrelateddirectlywithsubcutaneousfatthicknessandwas1.65-foldgreaterinwomenineachoftheselocations.Duflouetal30measuredEATthicknessin3selectedage-matchedgroupsofsubjects:group1-22massivelyobeseadults(meanweight,175I68kg;bodymassindex[BMI],57I12.8kg/m2[ISD],currentlyclassifiedasmorbidobesity)whodiedsuddenly;group2-6massivelyobeseadults(weight,131I25kg;
 
AmericanHearljournalVolume153,Number6
Sacks
andFain
909TableI.
CorrelationsbetweenepicardialandpericardialversusvisceralabdominalandSCATs
NS,
Nostatisticallysignificantcorrelation.'MeasuredusingMRI.tMeasuredusingCT.!Measuredasmediastinol(paracardiol)adiposetissue.§Measuredasparacardialplusepicardialadiposetissue.
BMI,45:t3.4kg/m2)whodiedofunnaturalcauses;group3-11nonobeseadults(weight,84:t24kg;BMI,27:t3.9kg/m2,currentlyclassifiedasoverweight)whodiedoftrauma.EpicardialfatwasmeasuredintheAVgroovesattherightandleftlateralbordersoftheheartandontheepicardialsurfaceoftheIVseptum,2cmdistaltotheoriginoftheleftanteriordescendingcoronaryartery.Thefollowingisanepicardialfatindex,calculatedasthemeanofthe3epicardialfatmeasurementstakenineachcase:group1,11:t3.2mm(:tSD);group2,11:t2.0mm;group3,
11
:t2.0mm.Thus,inthisautopsyseries,meanEATthicknessaroundthecoronaryarteriesdidnotdifferovertheBMIrangeof27to57kg/m2.TheirresultscannotbedirectlycomparedwiththoseofSchjebal's29becausetheirmeasurementsweremadeintheAVgroovesandtheanteriorIVseptumratherthantheRVfreewall,aswellasinpatientsselectedaccordingtobodyweightandmodeofdeathasopposedtoarandomlyselectedgroupofautopsypatients.RadiologyInhealthypeople(n
=
72)withBMI22to47kg/m2,
Iacobellisetal31usedECHOtomeasureepicardialfatandfoundthatthemaximalthicknessatanysiteoverthefreewalloftheRVvariedbetween1.8and16.5mm.TheseauthorsemphasizedthattheychosetomeasureepicardialfatontheRVfor2reasons:(i)thispointisrecognizedasthehighestabsoluteepicardialfatlayerthickness,and(ii)theiruseofparasternallong-andshort-axisviewsallowthemostaccuratemeasurementofEATontheRV,withoptimalcursorbeamorientationineachview.AlsousingECHO,Malvazosetal32reportedmeanEATvaluesonthefreewalloftheRVof1.3:t0.2mm(SD)in15healthylean(BMI,22:t1.7kg/m2)and6.5:t0.8mmin27healthyobese(BMI,43:t4.8kg/m2)women
(P
<.0001).Abbaraetal33pointoutthatECHOcannotgiveanadequatewindowofallcardiacsegmentsandishighlydependentonacousticwindows,whichareofteninadequateforsubtleassessmentsinobesepatients,resultinginaninsufficientexamination.34Abbaraetal33measuredEATusing16-slicescanner,multidetectorcomputerizedto-mography(MDCntoassessCADimagingin59adults(BMInotreported)inamappingstudydesignedtofacilitatetransepicardialarrhythmiaablation.TheMDCThasadvantagesofsubmillimetercollimation,hightem-poralandspatialresolution,and3-dimensionalviewsoftheheartanditsepicardialsurface.ThefollowingarethemeanEATthicknessatdifferentsitesindescendingorderofmagnitude:rightAVgroove,14.8mm;leftAVgroove,12.7mm;superiorIVgroove,11.2mm;inferiorIVgroove,9.2mm;acutemargin,9.2mm;anteriorIVgroove,7.7mm;RVanteriorfreewallinferior,6.8mm;RVanteriorfreewaJIsuperior,6.5mm;RVsuperiorwall,5.6mm;RVapex,4.8mm;LVapex,2.8mm;RVdiaphragmaticwall,1.4mm;andLVsuperiorlateralwall,1.0mm.MeanEATthicknessforallpatientswas5.3:t1.6mm(SD).TotalEATcontentwasonaverage22%greaterforpatientsmorethan65yearsofageand17%greaterinwomeninagreementwithanautopsyreport.29There-fore,inthiscohort,thethickestpartofEATwasinitsgroovedandnot,assomeauthors29"'1suggest,inthenongroovedsegmentsthatincludethefreewalloftheRV.
Study(n)8MI(kg/m2)RadiologicalmethodCorrelationsReference
Italian31Menandwomen(72)34.0:t14.5(SD)ECHOEATvsVAT':r
=0.84,
P
=.001
EATvsSCAT':NSItalian32Womenlean(15)22.6:tl.7(SD)ECHOEATvsVATt:r=0.80,
P
<.0001Womenobese(27)43.5:t4.8EATvsVAT/SCATt:r=0.74,
P
=.0001Italian15Men(23)27.7:t0.6(SEM)MRIEATvsVAT:NSPATtvsVAT:r=0.66,
P
<.0006PATtvsSCAT:NSAmerican14Menandwomen(80)31.9:t7.3(SD)
a
PAT§vsVAT:r=0.81,
P
<.0001PAT§vsSCAT:notreportedJapanese17Mennonobese(181)22.7i2.0(SD)
a
PAT§vsVAT:r=0.791,
P
<.001PAT§vsSCAT:r=0.470,
P
<.001Menobese(64)27.6:t2.3(SD)PAT§vsVAT:r=0.692,
P
<.001PAT§vsSCAT:r=0.410,
P
<.001

Activity (19)

You've already reviewed this. Edit your review.
1 hundred reads
1 thousand reads
biancushi liked this
omeganeu liked this
wonderfulrobot liked this
wonderfulrobot liked this
diemo_schaller liked this
Roslin Lin liked this
Sankar Mukherjee liked this

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->