Normal Endothelium -- Functional Ultrastructure of the Vascular Endothelium: Changes in Various Pathologies -- Development of the Endothelium -- Transport Across the Endothelium: Regulation of Endothelial Permeability -- Calcium Signalling in the Endothelium -- Eicosanoids and the Vascular Endothelium -- Nitric Oxide and the Vascular Endothelium -- Angiotensin, Bradykinin and the Endothelium -- Endothelin -- Transport Across the Endothelium: Regulation of Endothelial Permeability. It was with great pleasure that I accepted the invitation of Springer to edit thisbook.Myassociationwiththevascularendotheliumcoversalargepartof myscienti?ccareerand,aswithanygoodlong-standingrelationship,ithas had moments of great excitement and periods of laborious construction. It hassometimesbeendif?cultbuthasnevergivenmecausefordespondency. 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 signi?cant contributions in the ?eld agreed to write chapters; as aresult,wehaveproducedtwovolumeswhichisagoodrepresentationofour knowledgeinearly2006.Weare,however,awarethatthe?eldhasexpanded beyond all expectation and that there may have been some oversight in the covering of a speci?c 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 speci?c pathologies and their treatment.The?nalchapterdescribesvariousgene-therapystrategiesforthe treatmentofvascularpathologies.Interestingly,althoughthis?eldofresearch can now be considered mature, it continues to generate a great deal of new informationatatimewhensomeofitsfruitsarehavingadirectimpacton clinical medicine. This is clearly exempli?ed in the contents of most of the chapters. Theconceptofendothelialdysfunction,althoughmootedmanyyearsago, hascometotheforeandhasbeenveryusefulinde?ningasituationwhichmay existlongbeforetheovertsignsofvasculardiseasescanbeidenti?ed.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 pharmacologicalagonistsorbyincreasesinblood?ow.Oxidativestress,which isassociatedwiththegenesisofendothelialdysfunction,isaloosetermused tode?neanimbalancebetweenthereleaseofoxygen-derivedfreeradicalsand theanti-oxidantsystemsofthebody.Manyyearsagoourworkestablishedthat reactiveoxygenspeciesareimportantinreducingthelocalconcentrationsof bothprostacyclin and NO. It is now clear that free radicals also affect other homeostaticsystemsinthevasculature.However,manythingsremaintobe clari?ed,especiallytheoriginofoxidativestressinearlydisease.