Contrast enhanced ultrasound molecular imaging of platelets in the inflammatory procession of atherosclerosis / 中华超声影像学杂志

ABSTRACT

Objective To assess the role of activated platelets in the inflammatory procession of atherosclerosis(AS)by ultrasound molecular imaging.Methods Sixty ApoE-/-mice were fed with high fat diet to establish AS model as experimental group,and 40 C57BL/6J mice were fed with normal diet as control group.Biotin-avidin bridging method was used to construct platelet-targeted microbubbles with recombinant vWF-A1 domain (Mb-A1),microbubbles carrying monoclonal antibodies to VCAM-1 (Mb-VCAM1)and microbubbles carrying IgG monoclonal antibody(Mb-ctrl).In vitro and in vivo experiments were carried out to evaluate the ability of Mb-A1 to target platelets on vascular endothelial surface.Contrast enhanced ultrasound molecular imaging of proximal ascending aorta was performed with Mb-A1 ,Mb-VCAM1 and Mb-ctrl.The expression and distribution of platelets and monocytes/macrophages on the endothelium of ascending aorta of AS mice were observed and analyzed by immunofluorescence staining. Results ①A large number of Mb-A1 adhering to the surface of activated platelets coated in Petri dishes were observed under fluoresce.②After platelet immune-depletion in 30-week AS mice,the signal intensity of Mb-A1 decreased significantly in ascending aorta,while that of Mb-ctrl has no obvious change(P <0.05).③In ApoE-/-mice,signals from platelet targeted microbubbles increased from 8 to 32 weeks of age in ApoE-/-mice,which coincided with the increase of signals from VCAM-1 targeted microbubbles(P <0.05).④Activated platelets on the endothelial surface of ascending aorta increased progressively with age from 8 weeks,and partly overlapped with the distribution of monocytes/macrophages.Conclusions Platelets contribute to the initiation and progression of atherosclerosis as an inflammatory mediator through the interaction with vascular endothelium.