The possibility of visualizing TGF-β1 expression in ApoE−/− mice atherosclerosis using MR targeted imaging

Abstract

Background Endothelial TGF-β1 signaling is a primary driver of atherosclerosis-associated vascular inflammation. Targeted imaging and inhibition of the expression of TGF-β1 may reduce the atherosclerotic vessel wall inflammation and stop the progression of atherosclerotic plaque. Purpose To investigate the possibility of the anti-TGF-β1-ultrasmall superparamagnetic iron oxide (USPIO) specific probe as an imaging marker for the expression of TGF-β1 in ApoE–/– mice atherosclerosis detected with 7.0-T magnetic resonance imaging (MRI). Material and Methods Here, 70 ApoE–/– mice on a high-fat diet served as the experimental group and 30 C57BL/6 mice on a normal diet served as the control group. The morphology of plaques was viewed by H&E staining, and the expression and distribution of TNC and TGF-β1 were detected by immunohistochemical staining. Another 40 mice in the experimental group were classified into a targeted group, which was administrated an anti-TGF-β1-USPIO probe, and the pure group, which was injected with pure USPIO. Results The 7.0-T MRI showed that the relative signal intensity (rSI) changes of the targeted group decreased more than those of the pure group (−19.34 ± 0.68% vs. −5.61 ± 0.57%; P < 0.05). Histopathological analyses demonstrated expression of TGF-β1 in atherosclerotic plaque formation progression from 10 to 28 weeks. The MR images of the expression of TGF-β1 in atherosclerosis correlated well with the pathological progression of atherosclerotic plaque formation. Conclusions Anti-TGF-β1-USPIO could provide a useful molecular imaging tool for detecting and monitoring the expression of TGF-β1 in atherosclerotic plaques by MRI.