Retrospectively gated MRI for in vivo assessment of endothelium-dependent vasodilatation and endothelial permeability in murine models of endothelial dysfunction
Retrospectively gated MRI for in vivo assessment of endothelium-dependent vasodilatation and endothelial permeability in murine models of endothelial dysfunction
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DOI：
10.1002/nbm.3567
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发表时间：
2016-08-01
影响因子：
2.9
通讯作者：
Chlopicki, Stefan
中科院分区：
文献类型：
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作者：
Bar, Anna;Skorka, Tomasz;Chlopicki, Stefan
内皮功能障碍与内皮依赖性血管舒张和通透性变化受损有关。在这里，我们通过小鼠体内 MRI 来量化与内皮功能障碍相关的这两种现象。与对照小鼠 (C57BL/6J) 相比，对 ApoE/LDLR-/- 和高脂饮食 (HFD) 喂养的小鼠的头臂动脉 (BCA) 和左颈动脉 (LCA) 的内皮功能进行了评估。 3D IntraGate (R) FLASH 序列用于评估乙酰胆碱 (Ach) 给药后血管横截面积 (CSA) 和体积的变化。给予造影剂（白蛋白，BioPAL）后内皮通透性的评估基于可变翻转角方法，用于基于弛豫时间（T-1）值的参数评估。为了证实一氧化氮 (NO) 参与 Ach 反应，还对 L-NAME 治疗的小鼠进行了分析。为了证实内皮通透性变化伴随着 Ach 依赖性血管舒张功能的损害，我们对分离的灌注颈动脉的通透性变化进行了分析。在 C57BL/6J 小鼠中，Ach 诱导的血管舒张导致两条血管的 CSA 增加约 25%，这与 Ach 对心率的影响暂时无关。在 ApoE/LDLR-/- 或 HFD 喂养的小鼠中，Ach 诱导反常的血管收缩，使 BCA 和 LCA 的 CSA 分别减少约 30% 和 50%。在 ApoE/LDLR-/- 和 HFD 喂养的小鼠中，BCA 的内皮通透性也增加（T-1 下降约 25%）。在 L-NAME 治疗的小鼠中，Ach 诱导的 BCA 血管舒张功能消失。在来自 ApoE/LDLR-/- 小鼠的分离灌注动脉中，内皮通透性增加。使用回顾性自门控 3D 梯度回波序列 (IntraGate (R) FLASH) 基于 MRI 评估 Ach 诱导的内皮依赖性血管舒张和内皮通透性，能够可靠地检测小鼠的全身内皮功能障碍，并为体内疾病小鼠模型中内皮的实验药理学提供重要工具。版权所有 (C) 2016 约翰·威利父子有限公司
Endothelial dysfunction is linked to impaired endothelial-dependent vasodilatation and permeability changes. Here, we quantify both of these phenomena associated with endothelial dysfunction by MRI in vivo in mice.Endothelial function was evaluated in the brachiocephalic artery (BCA) and left carotid artery (LCA) in ApoE/LDLR-/- and high-fat diet (HFD)-fed mice as compared with control mice (C57BL/6J). The 3D IntraGate (R) FLASH sequence was used for evaluation of changes in vessels' cross-sectional area (CSA) and volume following acetylcholine (Ach) administration. Evaluation of endothelial permeability after administration of contrast agent (Galbumin, BioPAL) was based on the variable flip angle method for the assessment of parameters based on the relaxation time (T-1) value. In order to confirm the involvement of nitric oxide (NO) in response to Ach, L-NAME-treated mice were also analyzed. To confirm that endothelial permeability changes accompany the impairment of Ach-dependent vasodilatation, permeability changes were analyzed in isolated, perfused carotid artery.In C57BL/6J mice, Ach-induced vasodilatation led to an approximately 25% increase in CSA in both vessels, which was temporarily dissociated from the effect of Ach on heart rate. In ApoE/LDLR-/- or HFD-fed mice Ach induced a paradoxical vasoconstriction that amounted to approximately 30% and 50% decreases in CSA of BCA and LCA respectively. In ApoE/LDLR-/- and HFD-fed mice endothelial permeability in BCA was also increased (fall in T-1 by about 25%). In L-NAME-treated mice Ach-induced vasodilatation in BCA was lost. In isolated, perfused artery from ApoE/LDLR-/- mice endothelial permeability was increased.MRI-based assessment of endothelium-dependent vasodilatation induced by Ach and endothelial permeability using a retrospectively self-gated 3D gradient-echo sequence (IntraGate (R) FLASH) enables the reliable detection of systemic endothelial dysfunction in mice and provides an important tool for the experimental pharmacology of the endothelium in murine models of diseases in vivo. Copyright (C) 2016 John Wiley & Sons, Ltd.