Quantifying the Evolution of Vascular Barrier Disruption in Advanced Atherosclerosis with Semipermeant Nanoparticle Contrast Agents 英文参考文献.docVIP

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Quantifying the Evolution of Vascular Barrier Disruption in Advanced Atherosclerosis with Semipermeant Nanoparticle Contrast Agents 英文参考文献.doc

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Quantifying the Evolution of Vascular Barrier Disruption in Advanced Atherosclerosis with Semipermeant Nanoparticle Contrast Agents 英文参考文献

QuantifyingtheEvolutionofVascularBarrierDisruption inAdvancedAtherosclerosiswithSemipermeant NanoparticleContrastAgents HuiyingZhang1,LeiZhang1,JacobMyerson1,2,KristinBibee1,3,MichaelScott1,JohnAllen1 ,Gregorio Sicard4,GregoryLanza1,2,SamuelWickline1,2,3 * 1DepartmentofMedicine,WashingtonUniversity,StLouis,Missouri,UnitedStatesofAmerica,2DepartmentofBiomedicalEngineering,WashingtonUniversity,StLouis, Missouri, United States of America, 3Department of Cellular Biology, Washington University, St Louis, Missouri, United States of America, 4Department of Surgery, WashingtonUniversity,StLouis,Missouri,UnitedStatesofAmerica Abstract Rationale:Acuteatherothromboticocclusioninheartattackandstrokeimpliesdisruptionofthevascularendothelialbarrier thatexposesahighlyprocoagulantintimalmilieu.However,theevolution,severity,andpathophysiologicalconsequences of vascular barrier damage in atherosclerotic plaque remain unknown, in part because quantifiable methods and experimentalmodelsarelackingforitsinvivoassessment. Objective:Todevelopquantitativenondestructivemethodologiesandmodelsfordetectingvascularbarrierdisruptionin advancedplaques. MethodsandResults:SustainedhypercholesterolemiainNewZealandWhite(NZW)rabbitsfor.7–14monthsengendered endothelial barrier disruption that was evident from massive and rapid passive penetration and intimal trapping of perfluorocarbon-corenanoparticles(PFC-NP:,250nmdiameter)afterinvivocirculationforaslittleas1hour.Onlyolder plaques(.7mo),butnotyoungerplaques(,3mo)demonstratedthemarkedenhancementofendothelialpermeabilityto these particles. Electron microscopy revealed a complex of subintimal spongiform channels associated with endothelial apoptosis,superficialerosions,andsurface-penetratingcholesterolcrystals.Fluorine(19F)magneticresonanceimagingand spectroscopy (MRI/MRS) enabled absolute quantification (in nanoMolar) of the passive permeation of PFC-NP into the disruptedvascularlesionsbysensingtheuniquespectralsignaturesfromthefluorinecoreofplaque-bou