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.