Expression Of Tenascin-C In Mouse Atherosclerotic Plaques And Experimental Study Of Targeted MR In Vivo Imaging

Objective1.To investigate the dynamic changes of Tenascin-C expression at different phases(4,8,16,24,32w)of atherosclerosis in ApoE-/-mice,and to explore its expression characteristics.2.To investigate the possibility of the anti-Tenascin-C-USPIO specific probe as a marker of atherosclerotic plaques by MRI and provide experimental evidence for the clinical application of molecular imaging.Materials and methods1.Fifty ApoE-/-mice fed a high fat diet were used as atherosclerosis models,and fifty C57BL/6 mice fed a normal chow were used as controls.The mice were sacrificed at 4,8,16,24,32 weeks(w).Blood was collected for measuring lipid,aorta was prepared for morphologic study and immunohistochemical analysis of Tenascin-C.2.Twenty ApoE-/-mice fed a high fat diet were used for detecting the thoracic aorta atherosclerotic plaques by 7.0T MRI at 16 and 24 weeks.Ten mice were injected with anti-Tenascin-C-/-SPIO,and another 10 mice were inj ected with pure USPIO(n=5 each time point in each group).Immunohistochemical analysis was used to compare Tenascin-C expression.Prussian blue stain was used to prove the presence of iron particles.Results1.Serum cholesterol and low density lipoprotein levels were significantly higher in ApoE-/-group than in C57BL/6 group.Plaque area and ratio significantly increased with prolonged modeling time in ApoE-/-group.Tenascin-C expression reached the highest level at 32 weeks,and was significantly higher than that of 8,16,24 weeks(0.49±0.07 vs 0.04±0.02,0.12±0.03,0.21±0.04,P<0.05).2.The relative signal intensity(rSI)changes of the targeted group decreased more than that of the control group(16w:-15.65 ± 0.78%vs.-3.43 ± 2.57%;24w:-26.38 ±1.54%vs.-11.12 ± 1.60%,respectively;P<0.05);and,in the targeted group,rSI changed more in 24 w than in 16 w(P<0.05).Immunohistochemical examination showed that Tenascin-C expression increased with the development of atherosclerotic plaques from 16 to 24 weeks corresponding to MR images in the targeted group.Prussian blue stain showed more blue particles deposition in the plaques in the targeted group,while there was very few in the control group.Conclusion1.The expression of Tenascin-C increased with the progress of atherosclerosis,and it's mainly expressed around the lipid core and ruptured fibrous cap.The expression level of Tenascin-C may be associated with the development of atherosclerosis and the instability of plaques.2.The atherosclerotic plaques can be evaluated imaged by using 7.0T MRI in vivo.Anti-Tenascin-C-USPIO could provide a useful molecular imaging tool for detecting and monitoring atherosclerotic plaques in vivo and this method may lay the foundation for the further development of atherosclerotic molecular imaging.