Monitoring vascular permeability and remodeling after endothelial injury in a murine model using a magnetic resonance albumin-binding contrast agent.
Monitoring vascular permeability and remodeling after endothelial injury in a murine model using a magnetic resonance albumin-binding contrast agent.
复制标题
使用磁共振白蛋白结合造影剂监测小鼠模型中内皮损伤后的血管通透性和重塑。
DOI：
10.1161/circimaging.114.002417
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Botnar RM
中科院分区：
文献类型：
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作者：
Lavin B;Phinikaridou A;Lorrio S;Zaragoza C;Botnar RM
补充数字内容可在文本中找到。尽管血管介入治疗具有有益效果，但这些手术可能会损伤内皮，导致血管通透性增加和重塑。具有功能和结构完整细胞的血管壁的再内皮化由内皮型一氧化氮合酶（NOS 3）控制，并且对于减轻损伤后的不良反应至关重要。我们研究了白蛋白结合MR造影剂gadofosveset在体内非侵入性监测NOS 3敲除（NOS 3 −/−）和野生型（WT）小鼠损伤后血管通透性和重塑的局灶性变化的适用性。WT和NOS 3 −/−小鼠在主动脉剥脱或假手术后7、15和30天进行成像。T1标测（R1=1/T1，s-1）和延迟增强MRI分别用于测量注射钆磷维塞后的血管通透性（R1）和重塑（血管壁增强，mm 2）。与假手术动物相比，两种品系在损伤后7天剥脱导致更高的血管通透性和血管壁增强。然而，与显示再内皮化和缺乏新血管形成的WT小鼠相比，NOS 3 −/−小鼠中受损的再内皮化和增加的新血管形成导致损伤后15天和30天的R1显著更高（R1 [s−1]=15天：NOS 3 −/−4.02 [四分位距，IQR，3.77-4.41] vs WT 2.39 [IQR，2.35-2.92]; 30天：NOS3−/−4.23 [IQR，3.94-4.68] vs WT 2.64 [IQR，2.33-2.80]）。同样，血管壁增强在NOS 3 −/−中较高，但在WT小鼠中恢复（面积[mm 2]=15天：NOS 3 −/−5.20 [IQR，4.68-6.80] vs WT 2.13 [IQR，0.97-3.31]; 30天：NOS 3 −/−7.35 [IQR，5.66-8.61] vs WT 1.60 [IQR，1.40-3.18]）。离体组织学研究证实了MRI结果。我们证明，增加血管通透性和重塑，损伤后，可以评估非侵入性使用白蛋白结合MR造影剂，并可用作替代标记物，用于评估损伤后血管壁的愈合反应。
Supplemental Digital Content is available in the text. Despite the beneficial effects of vascular interventions, these procedures may damage the endothelium leading to increased vascular permeability and remodeling. Re-endothelialization of the vessel wall, with functionally and structurally intact cells, is controlled by endothelial nitric oxide synthase (NOS3) and is crucial for attenuating adverse effects after injury. We investigated the applicability of the albumin-binding MR contrast agent, gadofosveset, to noninvasively monitor focal changes in vascular permeability and remodeling, after injury, in NOS3-knockout (NOS3−/−) and wild-type (WT) mice in vivo. WT and NOS3−/− mice were imaged at 7, 15, and 30 days after aortic denudation or sham-surgery. T1 mapping (R1=1/T1, s−1) and delayed-enhanced MRI were used as measurements of vascular permeability (R1) and remodeling (vessel wall enhancement, mm2) after gadofosveset injection, respectively. Denudation resulted in higher vascular permeability and vessel wall enhancement 7 days after injury in both strains compared with sham-operated animals. However, impaired re-endothelialization and increased neovascularization in NOS3−/− mice resulted in significantly higher R1 at 15 and 30 days post injury compared with WT mice that showed re-endothelialization and lack of neovascularization (R1 [s−1]=15 days: NOS3−/−4.02 [interquartile range, IQR, 3.77–4.41] versus WT2.39 [IQR, 2.35–2.92]; 30 days: NOS3−/−4.23 [IQR, 3.94–4.68] versus WT2.64 [IQR, 2.33–2.80]). Similarly, vessel wall enhancement was higher in NOS3−/− but recovered in WT mice (area [mm2]=15 days: NOS3−/−5.20 [IQR, 4.68–6.80] versus WT2.13 [IQR, 0.97–3.31]; 30 days: NOS3−/−7.35 [IQR, 5.66–8.61] versus WT1.60 [IQR, 1.40–3.18]). Ex vivo histological studies corroborated the MRI findings. We demonstrate that increased vascular permeability and remodeling, after injury, can be assessed noninvasively using an albumin-binding MR contrast agent and may be used as surrogate markers for evaluating the healing response of the vessel wall after injury.