Atherosclerosis: Diet and Drugs

808 Pages·2005·8.193 MB·English

by  P. Cullen, J. Rauterberg, S. Lorkowski (auth.), Professor Dr. med. Arnold von Eckardstein (eds.)

Handbook of
Experimental Pharmacology
Volume 170
Editor-in-Chief
K.Starke,Freiburgi.Br.
EditorialBoard
G.V.R.Born,London
M.Eichelbaum,Stuttgart
D.Ganten,Berlin
F.Hofmann,München
W.Rosenthal,Berlin
G.Rubanyi,Richmond,CA
Atherosclerosis:
Diet and Drugs
Contributors
J.Ahrens,M.Anthony,T.Asahara,M.Aviram,S.Bellosta,
F.Bernini,C.Bode,C.Bolego,C.Bouchard,G.Chinetti,
A.Cignarella,R.St.Clair,P.Cullen,A.Dendorfer,P.Dominiak,
C.Fontaine,J.-C.Fruchart,B.Fuhrmann,G.Gabbiani,
J.Greeve,A.K.Groen,S.Grundy,H.Hendriks,M.Hersberger,
O.M.Hess,M.Kaplan,A.Kosters,K.M.Kostner,G.M.Kostner,
P.Kovanen,M.Kratz,F.Kuipers,T.Lakka,T.Lüscher,F.Mach,
R.Mensink,D.Müller-Wieland,R.Paoletti,K.Peters,
T.Plösch,R.Robillard,M.Rosenblatt,W.Schmitz,
H.Schunkert,B.Staels,R.Stocker,P.Suter,M.A.M.A.Thijssen,
M.Tikkanen,A.vanTol,E.Vähäkangas,A.vonEckardstein,
Q.Xu,S.Ylä-Herttuala
Editor
Arnold von Eckardstein
123
Professor
Dr.med.ArnoldvonEckardstein
InstituteofClinicalChemistry
UniversityHospitalofZurich
Rämistrasse100
8091Zürich
Switzerland
e-mail:[email protected]
With78Figuresand36Tables
ISSN0171-2004
ISBN-103-540-22569-2SpringerBerlinHeidelbergNewYork
ISBN-13978-3-540-22569-0SpringerBerlinHeidelbergNewYork
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Preface
Cardiovasculardiseasescontinuetobetheleadingcauseofdeathinthema-
jority of industrialized countries. The most frequent underlying pathology,
namely atherosclerosis, and its clinicalsequelae, namely coronary heart dis-
ease,cerebrovasculardiseaseandperipheralarterydisease,remaincommon
although for a long time we have been made aware of avoidable or modi-
fiable etiological factors such as smoking, fat-rich diet or lack of exercise,
and although these adverse lifestyle factors have been extensively addressed
bypopulation-wideprimarypreventionprograms.Cardiovascularmorbidity
andmortalityalsoremainhighdespitesuccessfulanti-hypertensiveandlipid
lowering drug therapies which help to reduce cardiovascular morbidity and
mortality by about 30% in both secondary and tertiary prevention settings.
Thiscanpartlybeexplainedbytheincreasinglifeexpectancyandgrowingpro-
portionofelderlypeople,especiallyinEuropeandNorthAmerica.Inaddition,
theWorldHealthOrganizationmakesthealarmingpredictionthatprobably
inresponsetothespreadingofwesterndietarybehaviorandlackofexercise
resultinginanincreasingprevalenceofdiabetes,dyslipidemiaandhyperten-
sion, cardiovasculardiseasesrather thaninfectiousdiseaseswill becomethe
mostfrequentcauseofdeathworldwide.
This volume of the Handbook of Experimental Pharmacology entitled
“Atherosclerosis” is divided into four parts and intends to give an overview
onthepathogenesisofatherosclerosis,establishedtreatmentandprevention
regimen,andofperspectivesforthedevelopmentofnewtreatmentmodalities.
The three chapters of part I review the state-of-the-art knowledge on the
pathogenesis of atherosclerosis and its underlying risk factors. Because of
its increasing prevalence and corresponding public health relevance, special
attentionisgiventothemetabolicsyndrome,i.e.totheclusteringofriskfactors
withinagivenindividual.Althoughtheexpressionofsingleriskfactorsinthis
situationmaybemoderate,affectedindividualsareathighriskforcoronary
heartdiseaseevents.Inaddition,duetotheimportantetiologicalcontribution
of obesity and overweight, the metabolic syndrome is an important reason
whyatherosclerosiscontinuestobeasignificantpublichealthburden.
TheninechaptersofpartIIaredevotedtotheroleofthevariousmajorand
minor components of diet in the pathogenesis of cardiovascular risk factors
andatherosclerosis.Thisfieldiscurrentlyexperiencingarenaissancefortwo
VI Preface
reasons:First,afterfatandnotablycholesterolhadbeenaccusedofbeing“the
badguys”foralongtime,novelresearchfindingsandtheepidemicofobesity
anddiabetesproducedamoredifferentiatedviewofthepathogeneticrelevance
ofthevariousdietarycompounds.Second,bothdrugandfoodindustryhave
discovereddietasatherapeutictargetandarecurrentlydevelopingdrugsfor
thetreatmentandpreventionofoverweightandfunctionalfoodsenrichedby
putativelycardioprotectivenutrients.
ThefourchaptersofpartIIIgiveanoverviewofgroupsofdrugswhichin
controlledinterventiontrialseffectivelypreventedatheroscleroticcardiovas-
cular disease, i.e. statins, fibrates, inhibitors of the renin-angiotensin system
andantiplateletagents.Unfortunately,beta-blockersarenotcovered,because
theauthorinchargeofthissubjectfinallywithdrewhiscommitment.
The14chaptersofpartIVpresentseveraltargetsandperspectivesfornovel
pharmacologicalinterventions.Someofthesestrategiesledtothere-evaluation
andoptimizationofdrugsalreadyonthemarket,forexamplenicotinicacidor
agonistsofperoxisomeproliferatingagentreceptors.Otherstrategieshelpedto
developdrugswhichareinphaseIIItrialsandwillprobablybeintroducedinto
themarketsoon,forexampleinhibitorsofcholesterylestertransferprotein.
Finally, some developments are still in the initial stage and must overcome
methodological limitations, such as gene therapy. Especially for this part IV
it is important to recall that atherosclerosis is a multifactorial disease which
consequentlyoffersmanytargetsfortreatment.Therefore,Ihopethatwedid
notleaveoutimportantdevelopments.Someauthorsunfortunatelywithdrew
theiroriginalcommitmenttowriteachapterforthisbooksothat,forexample,
importantcontroversiallydiscussedstrategies,likehormonereplacementand
antibiotictherapies,aremissing.
Lastbutnotleast,IwishtothankSpringerVerlagandtheEditorialBoard
for giving me the honour and chance to edit a “Handbook of Experimental
Pharmacology”onatherosclerosis.Iamverygratefultoallauthorsfor their
excellentcontributions.IalsothankMrs.BernadetteHand(Zurich)forcareful
language editing and Mrs. Susanne Dathe (Springer Verlag) for her patience
andhelpwhileaccompanyingmethroughthisproject.
Zurich,February2005 ArnoldvonEckardstein
ListofContents
PartI. Background
ThePathogenesisofAtherosclerosis . . . . . . . . . . . . . . . . . . . . 3
P.Cullen,J.Rauterberg,S.Lorkowski
RiskFactorsforAtheroscleroticVascularDisease . . . . . . . . . . . . 71
A.vonEckardstein
MetabolicSyndrome:TherapeuticConsiderations . . . . . . . . . . . . 107
S.M.Grundy
PartII. TheImpactofDiet
PhysicalActivity,ObesityandCardiovascularDiseases . . . . . . . . . 137
T.A.Lakka,C.Bouchard
FattyAcidsandAtheroscleroticRisk . . . . . . . . . . . . . . . . . . . 165
M.A.Thijssen,R.P.Mensink
DietaryCholesterol,AtherosclerosisandCoronaryHeartDisease. . . . 195
M.Kratz
PlantSterolsandStanols . . . . . . . . . . . . . . . . . . . . . . . . . . 215
M.J.Tikkanen
CarbohydratesandDietaryFiber . . . . . . . . . . . . . . . . . . . . . 231
P.M.Suter
DietaryAntioxidantsandParaoxonasesAgainstLDLOxidation
andAtherosclerosisDevelopment . . . . . . . . . . . . . . . . . . . . . 263
M.Aviram,M.Kaplan,M.Rosenblat,B.Fuhrman
Soy,IsoflavonesandAtherosclerosis. . . . . . . . . . . . . . . . . . . . 301
R.St.Clair,M.Anthony
VIII ListofContents
HomocysteineandBVitamins . . . . . . . . . . . . . . . . . . . . . . . 325
S.Cook,O.M.Hess
Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
H.F.J.Hendriks,A.vanTol
PartIII.Evidence-BasedAnti-AtheroscleroticDrugTherapy
LipidandNon-lipidEffectsofStatins . . . . . . . . . . . . . . . . . . . 365
R.Paoletti,C.Bolego,A.Cignarella
Fibrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389
R.Robillard,C.Fontaine,G.Chinetti,J.-C.Fruchart,B.Staels
ACEInhibitorsandAngiotensinIIReceptorAntagonists . . . . . . . . 407
A.Dendorfer,P.Dominiak,H.Schunkert
InhibitionofPlateletActivationandAggregation . . . . . . . . . . . . 443
I.Ahrens,C.Bode,K.Peter
PartIV.TargetsofFutureAnti-AtheroscleroticDrugTherapy
TheABCofHepaticandIntestinalCholesterolTransport . . . . . . . . 465
T.Plösch,A.Kosters,A.K.Groen,F.Kuipers
InhibitionoftheSynthesisofApolipoproteinB-Containing
Lipoproteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
J.Greeve
TherapyofHyper-Lp(a) . . . . . . . . . . . . . . . . . . . . . . . . . . 519
K.M.Kostner,G.M.Kostner
ModulationofHigh-DensityLipoproteinCholesterolMetabolism
andReverseCholesterolTransport . . . . . . . . . . . . . . . . . . . . 537
M.Hersberger,A.vonEckardstein
InhibitionofLipoproteinLipidOxidation. . . . . . . . . . . . . . . . . 563
O.Cynshi,R.Stocker
CorrectionofInsulinResistanceandtheMetabolicSyndrome . . . . . 591
D.Müller-Wieland,J.Kotzka
ProtectionofEndothelialFunction . . . . . . . . . . . . . . . . . . . . 619
L.E.Spieker,T.F.Lüscher
ListofContents IX
ModulationofSmoothMuscleCellProliferationandMigration:
RoleofSmoothMuscleCellHeterogeneity . . . . . . . . . . . . . . . . 645
M.-L.Bochaton-Piallat,G.Gabbiani
ModulationofMacrophageFunctionandMetabolism . . . . . . . . . . 665
S.Bellosta,F.Bernini
InflammationIsaCrucialFeatureofAtherosclerosis
andaPotentialTargettoReduceCardiovascularEvents . . . . . . . . . 697
F.Mach
AutoimmuneMechanismsofAtherosclerosis . . . . . . . . . . . . . . . 723
K.Mandal,M.Jahangiri,Q.Xu
DrugTherapiestoPreventCoronaryPlaqueRuptureandErosion:
PresentandFuture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 745
P.T.Kovanen,M.Mäyränpää,K.A.Lindstedt
ReciprocalRoleofVasculogenicFactorsandProgenitorCells
inAtherogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 777
T.Murayama,O.M.Tepper,T.Asahara
GeneTherapyofAtherosclerosis . . . . . . . . . . . . . . . . . . . . . 785
E.Vähäkangas,S.Ylä-Herttuala
SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 809
ListofContributors
(Addressesstatedatthebeginningofrespectivechapters)
Ahrens,I. 443 Jahangiri,M. 723
Anthony,M. 301
Asahara,T. 777 Kaplan,M. 263
Aviram,M. 263 Kosters,A. 465
Kostner,G.M. 519
Bellosta,S. 665 Kostner,K.M. 519
Bernini,F. 665 Kotzka,J. 591
Bochaton-Piallat,M.-L. 645 Kovanen,P.T. 745
Bode,C. 443 Kratz,M. 195
Bolego,C. 365 Kuipers,F. 465
Bouchard,C. 137
Lakka,T.A. 137
Lindstedt,K.A. 745
Chinetti,G. 389
Lorkowski,S. 3
Cignarella,A. 365
Lüscher,T.F. 619
Clair,R.St. 301
Cook,S. 325
Mäyränpää,M. 745
Cullen,P. 3
Müller-Wieland,D. 591
Cynshi,O. 563
Mach,F. 697
Mandal,K. 723
Dendorfer,A. 407
Mensink,R.P. 165
Dominiak,P. 407
Murayama,T. 777
Fontaine,C. 389
Paoletti,R. 365
Fruchart,J.-C. 389
Peter,K. 443
Fuhrman,B. 263
Plösch,T. 465
Gabbiani,G. 645 Rauterberg,J. 3
Greeve,J. 483 Robillard,R. 389
Groen,A.K. 465 Rosenblat,M. 263
Grundy,S.M. 107
Schunkert,H. 407
Hendriks,H.F.J. 339 Spieker,L.E. 619
Hersberger,M. 537 Staels,B. 389
Hess,O.M. 325 Stocker,R. 563