Share：
Share this content in WeChat
X
[Chinese][PDF]1011157
• Original Article •
OxLDL-targeted iron oxide particles for magnetic resonance detection of carotid atherosclerotic lesions in vivo
FU Ming-cui  WEN Song  LU Tong  LIU Dong-fang  ZHOU Guan-hui  AN Yan-li  LIAO Lei  JU Sheng-hong  TENG Gao-jun 

DOI:10.3969/j.issn.1674-8034.2011.05.003.


[Abstract] Objective: The aim of this study was to determine the role of oxLDL targeted iron oxide particles in atherosclerotic lesions imaging in carotid atherosclerosis lesions of apoE-/- mice.Materials and Methods: PEG coated USPIO was conjugated with anti-mouse-oxLDL antibodies to construct an anti-oxLDL-USPIO probe while IgG-USPIO and unconjugated USPIO was used as controls. All formulations were characterized by using TEM, DLS and ELISA. The model of perivascular collar in the left carotid in apoE-/- mice was used. The MRI was processed in pre-, 8 h and 24 h after tain vein injection of a 30 mg Fe/Kg dose of USPIO nanoparticles.Results: MRI of atherosclerotic lesion, as manifested by signal loss, was observed after administration of targeted USPIO at 8 h and 24 h, the percent of signal reduced was-30.4±16% and-34.7±19% while the IgG-USPIO, pure USPIO and inhibition group have limited signal reduction, the difference was significant, P<0.05. Immunohistochemistry confirmed the presence of oxLDL/CD68 and iron particles.Conclusion: This study demonstrates that anti-oxLDL-USPIO can be used in imaging atherosclerotic lesions within 24 hours. It suggests a clinically translatable platform for the detection of oxLDL in atherosclerotic plaque in vivo and will play a role in therapeutic evaluation of atherosclerotic carotid plaque.
[Keywords] Atherosclerosis；Antibody；oxLDL；Magnetic resonance imaging

FU Ming-cui Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

WEN Song Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

LU Tong Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

LIU Dong-fang Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

ZHOU Guan-hui Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

AN Yan-li Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

LIAO Lei Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

JU Sheng-hong Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

TENG Gao-jun* Department of Radiology, Zhong-Da Hospital, Southeast University, Nanjing 210009, China

*Correspondence to: Teng GJ, E-mail: gjteng@vip.sina.com

Conflicts of interest   None.

Received  2011-07-05
Accepted  2011-08-17
DOI: 10.3969/j.issn.1674-8034.2011.05.003
DOI:10.3969/j.issn.1674-8034.2011.05.003.

[1]
Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation, 2011, 123(4): e18-e209.
[2]
Fuster V, Moreno PR, Fayad ZA, et al. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol, 2005, 46(6): 937-954.
[3]
Tang T, Howarth SP, Miller SR, et al. Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI. Stroke, 2006, 7(9): 2266-2270.
[4]
Fayad ZA, Fuster V. The human high-risk plaque and its detection by magnetic resonance imaging. Am J Cardiol, 2001, 88(2): 42-45.
[5]
Fayad ZA. The assessment of the vulnerable atherosclerotic plaque using MR imaging: a brief review. Int J Cardiovasc Imaging, 2001, 17(3): 165-177.
[6]
Taylor J, Butcher M, Zeadin M, et al. Oxidized low-density lipoprotein promotes osteoblast differentiation in primary cultures of vascular smooth muscle cells by up-regulating Osterix expression in an Msx2-dependent manner. J Cell Biochem, 2011, 112(2): 581-588.
[7]
Zettler ME, Prociuk MA, Austria JA, et al. OxLDL stimulates cell proliferation through a general induction of cell cycle proteins. Am J Physiol Heart Circ Physiol, 2003, 284(2): 644-653.
[8]
Zhen L, Gao MY, Lei H. One-pot reaction to synthesize biocompatible magnetite nanoparticles. Adv mater, 2005, 17(8): 1001-1005.
[9]
Hu FQ, Zhou Z, Yu L, et al. Preparation of biocompatible magnetite nanocrystals for in vivo magnetic resonance detection of cancer. Adv mater, 2006, 18(19): 2553-2556.
[10]
von der Thusen JH, van Berkel TJ, Biessen EA. Induction of rapid atherogenesis by perivascular carotid collar placement in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Circulation, 2001, 103(8): 1164-1170.
[11]
Trivedi RA, Mallawarachi C, JM UK-I, et al. Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arterioscler Thromb Vasc Biol, 2006, 26(7): 1601-1606.
[12]
Trivedi RA, JM UK-I, Graves MJ, et al. In vivo detection of macrophages in human carotid atheroma: temporal dependence of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI. Stroke, 2004, 35(7): 1631-1635.
[13]
Tang TY, Patterson AJ, Miller SR, et al. Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques. Neuroradiology, 2009, 51(7): 457-465.
[14]
Taratula O, Garbuzenko O, Savla R, et al. Multifunctional nanomedicine platform for cancer specific delivery of siRNA by superparamagnetic iron oxide nanoparticles-dendrimer complexes. Curr Drug Deliv, 2011, 8(1): 59-69.
[15]
Matsuura E, Hughes GR, Khamashta MA. Oxidation of LDL and its clinical implication. Autoimmun Rev, 2008, 7(7): 558-566.
[16]
Ishigaki Y, Katagiri H, Gao J, et al. Impact of plasma oxidized low-density lipoprotein removal on atherosclerosis. Circulation, 2008, 118(1): 75-83.
[17]
Tsimikas S, Shortal BP, Witztum JL, et al. In vivo uptake of radiolabeled MDA2, an oxidation-specific monoclonal antibody, provides an accurate measure of atherosclerotic lesions rich in oxidized LDL and is highly sensitive to their regression. Arterioscler Thromb Vasc Biol, 2000, 20(3): 689-697.
[18]
Shaw PX, Horkko S, Tsimikas S, et al. Human-derived anti-oxidized LDL autoantibody blocks uptake of oxidized LDL by macrophages and localizes to atherosclerotic lesions in vivo.Arterioscler Thromb Vasc Biol, 2001, 21(8): 1333-1339.
[19]
Torzewski M, Shaw PX, Han KR, et al. Reduced in vivo aortic uptake of radiolabeled oxidation-specific antibodies reflects changes in plaque composition consistent with plaque stabilization. Arterioscler Thromb Vasc Biol, 2004, 24(12): 2307-2312.
[20]
Briley-Saebo KC, Shaw PX, Mulder WJ, et al. Targeted molecular probes for imaging atherosclerotic lesions with magnetic resonance using antibodies that recognize oxidation-specific epitopes. Circulation, 2008, 117(25): 3206-3215.
[21]
Briley-Saebo KC, Cho YS, Shaw PX, et al. Targeted iron oxide particles for in vivo magnetic resonance detection of atherosclerotic lesions with antibodies directed to oxidation-specific epitopes. J Am Coll Cardiol, 2011, 57(3): 337-347.

PREV Evaluation of CLT1-(Gd-DTPA) for MR molecular imaging in a mouse breast cancer model
NEXT Magnetic resonance imaging of injected adipose derived stem cells (ADSCs) in rat myocardial infarction: the feasibility of cell tracking and left ventricular function measurement in vivo
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn