The Complex Fate in Plasma of Gadolinium Incorporated into High-Density Lipoproteins Used for Magnetic Imaging of Atherosclerotic Plaques
The Complex Fate in Plasma of Gadolinium Incorporated into High-Density Lipoproteins Used for Magnetic Imaging of Atherosclerotic Plaques
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DOI：
10.1021/bc400105j
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发表时间：
2013-06-01
影响因子：
4.7
通讯作者：
Fisher, Edward A.
中科院分区：
文献类型：
--
作者：
Barazza, Alessandra;Blachford, Courtney;Fisher, Edward A.
我们以前曾报道过使用重组高密度脂蛋白（HDL）作为MRI造影剂钆（Gd）的纳米载体增强小鼠动脉粥样硬化斑块的成像。本研究的重点是Gd输送到动脉粥样硬化斑块的潜在机制。高密度脂蛋白，低密度脂蛋白，极低密度脂蛋白颗粒含有钆螯合磷脂酰乙醇胺（DTPA-DMPE）和一个无菌的荧光团被用来证明在体外和体内的血浆脂蛋白之间的Gd-磷脂的转移。为了确定这种转移的基础，磷脂转移蛋白（PLTP）和脂蛋白脂酶（LpL）介导的Gd-DTPA-DMPE之间的脂蛋白迁移的作用进行了研究。结果表明，这两个因素都不是重要因素，提示Gd-DTPA-DMPE的自发转移是最可能的机制。最后，使用两个独立的小鼠模型来量化用Gd-DTPA-DMPE重建的HDL和LDL对通过MR的斑块成像增强的相对贡献。两组结果表明，最初与LDL相关的Gd-DTPA-DMPE的有效性是以Gd-HDL形式注射的有效性的两倍，并且Gd-HDL在体内的一些有效性是通过将成像剂转移到LDL间接的。总之，与特定类型脂蛋白相关的Gd-DTPA-DMPE的命运是复杂的，包括其转移到其他脂蛋白种类，然后从血浆中清除到组织中。
We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL, and VLDL particles containing Gd chelated to phosphatidyl ethanolamine (DTPA-DMPE) and a lipidic fluorophore were used to demonstrate the transfer of Gd-phospholipids among plasma lipoproteins in vitro and in vivo. To determine the basis of this transfer, the roles of phospholipid transfer protein (PLTP) and lipoprotein lipase (LpL) in mediating the migration of Gd-DTPA-DMPE among lipoproteins were investigated. The results indicated that neither was an important factor, suggesting that spontaneous transfer of Gd-DTPA-DMPE was the most probable mechanism. Finally, two independent mouse models were used to quantify the relative contributions of HDL and LDL reconstituted with Gd-DTPA-DMPE to plaque imaging enhancement by MR Both sets of results suggested that Gd-DTPA-DMPE originally associated with LDL was about twice as effective as that injected in the form of Gd-HDL, and that some of Gd-HDL's effectiveness in vivo is indirect through transfer of the imaging agent to LDL. In conclusion, the fate of Gd-DTPA-DMPE associated with a particular type of lipoprotein is complex, and includes its transfer to other lipoprotein species that are then cleared from the plasma into tissues.