The Relationship Between Tenascin-C, Matrix Metalloproteinase-9, Transforming Growth Factor-?1 And Mouse Aortic Plaque And The Experimental Study Of Transforming Growth Factor-?1 Targeting MR In Vivo Imaging

Objective1.To dynamic observe the expression of TN-C,MMP-9 and TGF-?1 and the relationship with aorta atherosclerotic plaque stability on long-term high fat diet in Apo E-/-mice..2.Anti-TGF-?1-USPIO were synthesized by chemical coupling method,to investigate the feasibility of the targeted probe as a marker of Apo E-/-mice aortic atherosclerotic plaques by MRI in vivo.Materials and methods1.Forty male Apo E-/-mice on high fat diet served as experimental group and forty male C57BL/6 mice on basic fat diet served as control group.The morphology of plaques was observed with HE staining and the expression of TN-C,MMP-9 and TGF-?1 was detected with immunohistochemical staining.2.Twenty male Apo E-/-mice were fed with high fat diet for 28 weeks to establish an atherosclerotic model.Ultrafine superparamagnetic iron oxide(USPIO)was coated with polyethylene glycol(PEG),anti-TGF-?1-USPIO targeted probe was synthesized by binding anti-mouse TGF-?1 antibody on the surface USPIO coated with PEG.Pure USPIO was used as control group.The physical and specific characteristics of the probe were analyzed by electron microscopy(TEM),dynamic light scattering(DLS),enzyme-linked immunosorbent assay(ELISA).Ten mouses were injected with anti-TGF-?1-USPIO,and another 10 mouses were injected with pure USPIO,7.0T MR imaging was performed before and 24 h after injection.The aortic specimen was taken immediately after imaging,HE staining,immunohistochemical staining and prussian blue staining were performed to observe the morphology of the plaques,the expression of TGF-?1 and the deposition of iron in the plaques.Results1.The serum TC and LDL-C levels were significantly higher in experimental group than in control group at weeks 16,24,32 and 40(P<0.05).The serum TG level was significantly higher in experimental group than in control group at weeks 16(P<0.05)and was significantly lower in experimental group than in control group at weeks 40(P<0.05).With the lengthening of the feeding time,the plaque area,the ratio of plaque to lumen area,and the expression of TN-C and MMP-9 increased gradually,but the expression of TGF-?1 decreased gradually(P<0.05).2.The relative signal intensity(rSI)changes of the targeted group decreased more than that of the control group(-19.34 ± 0.68% vs-5.61 ± 0.57%;P<0.05).Immunohistochemical examination showed development of atherosclerotic plaques corresponding to MR images.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.With the evolution of time,the expression of TN-C and MMP-9 increased with the progression of plaque,and the expression of TGF-?1 decreased with the progression of plaque.The expression of TN-C,MMP-9 and TGF-?1 can show the stability of atherosclerotic plaque.2.Anti-TGF-?1-USPIO could can specifically display the expression of TGF-?1 in atherosclerotic plaques of aorta,it is helpful to monitor the progress of atherosclerotic plaques in vivo and provide experimental basis for evaluating the stability of atherosclerotic plaques.