The Vascular Endothelium II PDF
Preview The Vascular Endothelium II
Handbook of Experimental Pharmacology Volume 176/II Editor-in-Chief K.Starke,Freiburgi.Br. EditorialBoard G.V.R.Born,London S.P.Duckles,Irvine,CA M.Eichelbaum,Stuttgart D.Ganten,Berlin F.Hofmann,München W.Rosenthal,Berlin G.Rubanyi,SanDiego,CA The Vascular Endothelium II Contributors M.Aikawa,J.Arnout,C.Boshoff,R.Busse,P.Carmeliet, V.Dzau,J.D.Erusalimsky,C.Fischer,A.J.Flammer,I.Fleming, G.Garc´ıa-Carden˜a, M.A.GimbroneJr.,M.F.Hoylaerts, M.K.Jain,D.J.Kurz,K.Ley,P.Libby,H.R.Lijnen,T.F.Lüscher, L.G.Melo,W.Min,L.Nikitenko,A.S.Pachori,J.S.Pober, J.Reutershan,M.Schneider,L.E.Spieker Editors Salvador Moncada and Annie Higgs 123 Prof. Ms. SalvadorMoncada AnnieHiggs FRCPFRS TheWolfsonInstitute TheWolfsonInstitute forBiomedicalResearch forBiomedicalResearch UniversityCollegeLondon UniversityCollegeLondon GowerStreet GowerStreet LondonWC1E6BT LondonWC1E6BT UK UK E-mail:[email protected] E-mail:[email protected] With46Figuresand12Tables ISSN 0171-2004 ISBN-10 3-540-36027-1 SpringerBerlinHeidelbergNewYork ISBN-13 978-3-540-36027-8 SpringerBerlinHeidelbergNewYork Thisworkissubjecttocopyright.Allrightsreserved,whetherthewholeorpartofthematerialis concerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broad- casting,reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Duplicationof thispublicationorpartsthereofispermittedonlyundertheprovisionsoftheGermanCopyrightLaw ofSeptember9,1965,initscurrentversion,andpermissionforusemustalwaysbeobtainedfrom Springer.ViolationsareliableforprosecutionundertheGermanCopyrightLaw. SpringerisapartofSpringerScience+BusinessMedia springer.com ©Springer-VerlagBerlinHeidelberg2006 Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoesnot imply, even in the absence of a specific statement, thatsuch names are exempt from the relevant protectivelawsandregulationsandthereforefreeforgeneraluse. Productliability:Thepublisherscannotguaranteetheaccuracyofanyinformationaboutdosageand applicationcontainedinthisbook.Ineveryindividualcasetheusermustchecksuchinformationby consultingtherelevantliterature. Editor:SimonRallison,Heidelberg DeskEditor:SusanneDathe,Heidelberg Coverdesign:design&productionGmbH,Heidelberg,Germany Typesettingandproduction:LE-TEXJelonek,Schmidt&VöcklerGbR,Leipzig,Germany Printedonacid-freepaper 27/3100-YL-543210 Preface It was with great pleasure that I accepted the invitation of Springer to edit thisbook.Myassociationwiththevascularendotheliumcoversalargepartof my scientific career and, as with any good long-standing relationship, it has had moments of great excitement and periods of laborious construction. It hassometimesbeendifficultbuthasnevergivenmecausefordespondency. Indeed,inthelastquarterofacentury,researchonthevascularendothelium hasbeenveryproductiveanditsresultshavecontributed,arguablymorethan any others, to unravelling the mystery of cardiovascular disease, its origin, itsdevelopment,itscomplicationsanditspreventionortreatmentonceithas developed. IamveryhappythatAnnieHiggsagreedtojoinmeinthistask.Overthe yearswehavecollaboratedcloselyand,asalways,shehasshoulderedthebrunt oftheworkandhasmadesurethatthingsgetdonetoeverybody’ssatisfaction. We have also been fortunate in that the scientists who have made some of the most significant contributions in the field agreed to write chapters; as aresult,wehaveproducedtwovolumeswhichisagoodrepresentationofour knowledgeinearly2006.Weare,however,awarethatthefieldhasexpanded beyond all expectation and that there may have been some oversight in the covering of a specific area or some aspect of it. This is compounded by the speed at which knowledge is being generated, with more than 4,100 papers concerningtheendotheliumpublishedin2005. Thesevolumesareorganisedinsuchawaythattheearlychaptersdiscussthe structure,developmentandfunctionofthenormalvascularendothelium.The subsequent chapters consider conditions that lead to disruption of vascular physiology, while the later chapters deal with specific pathologies and their treatment.Thefinalchapterdescribesvariousgene-therapystrategiesforthe treatmentofvascularpathologies.Interestingly,althoughthisfieldofresearch can now be considered mature, it continues to generate a great deal of new information at a time when some of its fruits are having a direct impact on clinical medicine. This is clearly exemplified in the contents of most of the chapters. Theconceptofendothelialdysfunction,althoughmootedmanyyearsago, hascometotheforeandhasbeenveryusefulindefiningasituationwhichmay existlongbeforetheovertsignsofvasculardiseasescanbeidentified.Although VI Preface endothelial dysfunction is likely to comprise a variety of disturbances, it is interesting that these days it is almost exclusively measured as a decrease innitricoxide(NO)-dependentvasculardilatation,eitherinducedbysuitable pharmacologicalagonistsorbyincreasesinbloodflow.Oxidativestress,which isassociatedwiththegenesisofendothelialdysfunction,isaloosetermused todefineanimbalancebetweenthereleaseofoxygen-derivedfreeradicalsand theanti-oxidantsystemsofthebody.Manyyearsagoourworkestablishedthat reactiveoxygenspeciesareimportantinreducingthelocalconcentrationsof both prostacyclin and NO. It is now clear that free radicals also affect other homeostatic systems in the vasculature. However, many things remain to be clarified,especiallytheoriginofoxidativestressinearlydisease. Theabsenceofoneofthesemediators,inthiscasenotNO,butprostacyclin, has been discussed in the scientific and popular press for the past couple of years. The reason is that it is very likely that the cardiovascular side effects which have led to the withdrawal from the market of the anti-inflammatory classofdrugsknownasCOXIIinhibitorsareduetotheirinhibitoryactionon thegenerationofprostacyclinbythevasculature,leadingtoapro-thrombotic situation. The fact that reducing prostacyclin formation in the vasculature leadseventuallytocardiovasculareventsvalidatestheconceptweproposedin 1976thatabalancebetweenthegenerationofthromboxaneA bytheplatelets 2 andprostacyclinbythevesselwallissignificantindefiningthepro-oranti- thromboticstatusofthecardiovascularsystem.Previously,theonlyevidence availablecamefromtheactionoflow-doseaspirinwhich,byinhibitingplatelet thromboxane A without affecting prostacyclin, leads to an anti-thrombotic 2 situation.Thisraisestheissueaboutthestatusofacardiovascularsystemin which both prostacyclin and thromboxane A are inhibited following long- 2 termadministrationoftheclassicalCOXIinhibitors,somethingwhichweare onlynowbeginningtoaddress. The above are just a few considerations that exemplify the problems and challengesthatoccupyagreatdealofourattentiontoday.Theyshowthatthe vascular endothelium has moved a long way from the “cellophane wrapper” described by early vascular biologists to being recognised as an organ with avarietyoffunctions,someofwhich,Iamsure,remaintobedefined.What hasyettobediscoveredpromisestobeasexcitingandrewardingasthatwhich wealreadyknow. London, S.Moncada March2006 ListofContents Haemostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 J.Arnout,M.F.Hoylaerts,H.R.Lijnen VascularEndotheliumandBloodFlow . . . . . . . . . . . . . . . . . . 43 R.Busse,I.Fleming BiomechanicalModulationofEndothelialPhenotype: ImplicationsforHealthandDisease . . . . . . . . . . . . . . . . . . . . 79 G.García-Cardeña,M.A.GimbroneJr. Leukocyte-EndothelialInteractionsinHealthandDisease . . . . . . . 97 K.Ley,J.Reutershan EndothelialCellDysfunction,InjuryandDeath . . . . . . . . . . . . . 135 J.S.Pober,W.Min PrinciplesandTherapeuticImplicationsofAngiogenesis, VasculogenesisandArteriogenesis . . . . . . . . . . . . . . . . . . . . 157 C.Fischer,M.Schneider,P.Carmeliet EndothelialCellSenescence . . . . . . . . . . . . . . . . . . . . . . . . 213 J.D.Erusalimsky,D.J.Kurz TheVascularEndotheliuminHypertension . . . . . . . . . . . . . . . 249 L.E.Spieker,A.J.Flammer,T.F.Lüscher VascularEndotheliumandAtherosclerosis . . . . . . . . . . . . . . . . 285 P.Libby,M.Aikawa,M.K.Jain EndothelialCellsandCancer . . . . . . . . . . . . . . . . . . . . . . . 307 L.Nikitenko,C.Boshoff GeneTherapy:RoleinMyocardialProtection . . . . . . . . . . . . . . 335 A.S.Pachori,L.G.Melo,V.J.Dzau SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 VIII ListofContents ContentsofCompanionVolume176/I NormalEndothelium . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 A.R.Pries,W.M.Kuebler FunctionalUltrastructureoftheVascularEndothelium: ChangesinVariousPathologies . . . . . . . . . . . . . . . . . . . . . . 41 M.Simionescu,F.Antohe DevelopmentoftheEndothelium . . . . . . . . . . . . . . . . . . . . . 71 A.M.Suburo,P.A.D’Amore TransportAcrosstheEndothelium: RegulationofEndothelialPermeability . . . . . . . . . . . . . . . . . . 107 R.D.Minshall,A.B.Malik CalciumSignallingintheEndothelium . . . . . . . . . . . . . . . . . . 145 Q.-K.Tran,H.Watanabe EicosanoidsandtheVascularEndothelium . . . . . . . . . . . . . . . . 189 K.Egan,G.A.FitzGerald NitricOxideandtheVascularEndothelium. . . . . . . . . . . . . . . . 213 S.Moncada,E.A.Higgs Angiotensin,BradykininandtheEndothelium . . . . . . . . . . . . . . 255 C.Dimitropoulou,A.Chatterjee,L.McCloud,G.Yetik-Anacak J.D.Catravas Endothelin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 A.P.Davenport,J.J.Maguire SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 ListofContributors Addressesgivenatthebeginningofrespectivechapters Aikawa,M.,285 Jain,M.K.,285 Arnout,J.,1 Kurz,D.J.,213 Boshoff,C.,307 Ley,K.,97 Busse,R.,43 Libby,P.,285 Lijnen,H.R.,1 Carmeliet,P.,157 Lüscher,T.F.,249 Dzau,V.J.,335 Melo,L.G.,335 Min,W.,135 Erusalimsky,J.D.,213 Nikitenko,L.,307 Fischer,C.,157 Flammer,A.J.,249 Pachori,A.S.,335 Fleming,I.,43 Pober,J.S.,135 García-Cardeña,G.,79 Reutershan,J.,97 Gimbrone,M.A.,79 Schneider,M.,157 Hoylaerts,M.F.,1 Spieker,L.E.,249 HEP(2006)176/II:1–41 ©Springer-VerlagBerlinHeidelberg2006 Haemostasis J.Arnout·M.F.Hoylaerts·H.R.Lijnen((cid:1)) CentreforMolecularandVascularBiology,KULeuven,CampusGasthuisberg,O&N,1, Box911,Herestraat49,3000Leuven,Belgium [email protected] 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2 PlateletsinHaemostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.1 VonWillebrandFactor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2.1.1 StructureofvWF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.1.2 FunctionofvWF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2.1.3 vWF-GPIb/IX/VInteractionsinArterialThrombogenesis . . . . . . . . . . . 5 2.2 TheGPIbComplexasaPlateletReceptorforvWF. . . . . . . . . . . . . . . . 5 2.2.1 GPIb/IX/VOrganisation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.2.2 GPIbMediatedPlateletActivation . . . . . . . . . . . . . . . . . . . . . . . . 6 2.3 PlateletCollagenReceptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 α β 2.3.1 Integrin Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2 1 α β 2.3.2 RecognitionSiteinCollagenforIntegrin . . . . . . . . . . . . . . . . . . 7 2 1 2.3.3 GPVIonPlatelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.4 SecondaryPlateletRecruitmentandAggregation . . . . . . . . . . . . . . . . 9 2.5 LessonsfromDisease:LossandGainofFunction . . . . . . . . . . . . . . . . 10 2.5.1 Bernard–SoulierSyndromeandPlatelet-TypeVonWillebrandDisease . . . . 10 2.5.2 VonWillebrandDisease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.5.3 CollagenReceptorDeficiencyandBleeding . . . . . . . . . . . . . . . . . . . 11 2.6 InhibitionofPlateletDepositionontheVesselWall . . . . . . . . . . . . . . . 11 3 CoagulationSystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 3.1 StructureoftheMainProcoagulantandAnticoagulantProteins . . . . . . . . 13 3.1.1 SignalPeptide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 γ 3.1.2 Propeptide/ -CarboxyglutamicAcid-RichDomain . . . . . . . . . . . . . . . 16 3.1.3 EpidermalGrowthFactorDomain . . . . . . . . . . . . . . . . . . . . . . . . 16 3.1.4 KringleDomain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 3.1.5 CatalyticDomain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 3.1.6 Pseudosubstrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3.2 ProcoagulantMechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3.2.1 InitiationofCoagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3.2.2 Blood-BorneTissueFactor . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.2.3 PropagationofCoagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.2.4 BloodCoagulationasaSurface-CatalysedProcess . . . . . . . . . . . . . . . 20 3.3 AnticoagulantMechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 4 Fibrinolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 4.1 RegulationofPhysiologicalFibrinolysis . . . . . . . . . . . . . . . . . . . . . 24 4.1.1 PlasminogenActivationbyt-PA . . . . . . . . . . . . . . . . . . . . . . . . . 26 4.1.2 PlasminogenActivationbyu-PA . . . . . . . . . . . . . . . . . . . . . . . . . 26
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