inducetheformationof newblood vessels, isoneofthe mostpromisingtargetsforgenetherapy. Thisstrategy might playa majorroleinthetreatment of stroke, myocardialinfarction, limbischemiaand diabeticvascularcomplications—disabling problems that afflict millions of patientseach yearandare oftenfatal. Toinduceangiogenesis, investigatorshavedeliveredvascularendothelial growth factor (VEGF) or basic fibroblastgrowthfactor (bFGF/FGF2) asrecombinantproteinsorgenesusingplasmid DNA and viral vectors. Protein deliveryhasnotbeenhighlysuccessfulin clinicaltrialsandthe mostpromisingresultstodatehavebeenobtainedviagene therapy. Thisapproachenlistscellsofthe bodyto producetheirowntherapeutic proteinsusingthegeneticcodeofthedeliveredDNA. Forexample, directintramyocardial injection of plasmid DNA encodingVEGF165oradenoviraldeliveryof VEGF121 inpatients withseverecoronary arterydisease havebothyieldedsignificantimprovementofanginalsymptoms andcardiacfunction1, 2. Althoughthese clinicalresultsareencouraging, inthat theydemonstratethepotencyofasingle typeof molecule, conclusiveevidenceof benefitmustcomefromdouble-blind, randomized, placebo-controlled trials. Moreover, methodsforregulatedexpressionareattractive, giventhatanimalstudiesshowthatdeliveryof ‘too muchofa goodthing’(suchas VEGF) is deleterious3–5. Althoughearlystudiesfocusedon endothelialcellsandthepossibilityofinducingthemtoformnewstructures, recently it has become clear that the subsequentstagesofremodelingandstabilizationarecrucialtoattainingstableand functionalvessels. Accordingly, attention tothenecessarybalanceofbothcelltypes and moleculesinvessel maturationisimpactingthedesignofnoveltherapeuticangiogenicstrategies.