Author + information
- Yuyu Yao,
- Bing Li,
- Cong Fu and
- Genshan Ma
Background: Evidences have indicated that connective tissue growth factor (CTGF) plays an important role in the progression of atherosclerosis. Here we report a sensitive, specific CTGF-targeted ultrasmall superparamagnetic iron oxide (USPIO) for the noninvasive MR imaging of CTGF within carotid atherosclerotic lesions in apoE-/-, investigate the potential of anti-CTGF therapy in plaque formation, identify CTGF in human plaques.
Methods: anti-mouse CTGF polyclonal antibody & nonspecific IgG antibody were conjugated to polyethylene glycol-coated USPIO nanoparticles, a carotid partial ligation model in apoE-/- mice was imaged at 7.0 Tesla MRI before contrast administration & at 24 h after injection of 10 mg Fe/kg. Prussian blue staining was performed to demonstrate USPIOs deposition, with CTGF or macrophage marker, detected by immunohistochemistry. ApoE-/- mice were treated with an antibody to CTGF for an additional 3 weeks. Serial cross-sections of 10 human carotid plaques were immunohistochemically analyzed for the presence of CTGF protein, macrophages.
Results: In vitro analysis showed higher uptake of iron in macrophages treated with anti-CTGF-USPIO than those treated with IgG-USPIO, unconjugated USPIO & competitive inhibitor. MRI signal loss in the carotid atherosclerotic lesions after administration of targeted anti-CTGF-USPIO at 24 h, which is consistent with the presence of the nanoparticles in the lesions. Immunohistochemistry confirmed the colocalization of the CTGF/macrophages & nanoparticles. The IgG-USPIO, competitive inhibition groups had limited signal changes (p<0.05). Atheromata of anti CTGF-treated mice showed reduced macrophages deposition & CTGF expression as well as plaque volume. CTGF accumulated particularly in the rupture-prone plaque shoulder & co-stained positive for inflammatory cells in human plaque.
Conclusions: This report demonstrated that anti-CTGF-USPIO nanoparticles can be used to directly detect CTGF & image atherosclerotic lesions & suggests a strategy for the therapeutic evaluation of atherosclerotic plaques in vivo. CTGF is a potential target for clinical imaging & a therapy target for treatment atherosclerosis.
Moderated Poster Contributions
Vascular Medicine Moderated Poster Theater, Poster Hall, Hall C
Sunday, March 19, 2017, 1:00 p.m.-1:10 p.m.
Session Title: Mechanisms of Vascular Inflammation in Atherogenesis
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1320M-07
- 2017 American College of Cardiology Foundation