Department of Nuclear Medicine, University Hospital RWTH Aachen, 52074 Aachen, Germany.
Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
Cells. 2021 Jan 30;10(2):275. doi: 10.3390/cells10020275.
Given the high sensitivity and specificity of sodium [F]Fluoride (Na[F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet. The Menaquinone-7 (MK-7) and Warfarin groups received MK-7 or Warfarin supplementation during the additional 12-weeks, respectively. Control wild type mice were fed a chow diet for 24-weeks. All of the mice were scanned with Na[F]F using a small animal positron emission tomography (PET)/computed tomography (CT). The Warfarin group presented spotty calcifications on the CT in the proximal aorta. All of the spots corresponded to dense mineralisations on the von Kossa staining. After the control, the MK-7 group had the lowest Na[F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[F]F uptake was still observed, suggesting the presence of micro-calcifications. In a newly applied mouse model, developing spotty calcifications on CT exclusively in the proximal aorta, Na[F]F seems to efficiently monitor plaque progression and the beneficial effects of vitamin K on cardiovascular disease.
鉴于氟[F]酸钠(Na[F]F)对血管钙化的高灵敏度和特异性,以及维生素 K 对血管健康的积极新兴数据,本研究旨在评估 Na[F]F 在单一动脉粥样硬化小鼠模型中监测治疗和疾病进展的能力。载脂蛋白 E (ApoE) 小鼠接受西方型饮食 12 周,然后分为四组。早期动脉粥样硬化组接受普通饮食 12 周,而晚期动脉粥样硬化组继续接受西方型饮食。甲萘醌-7(MK-7)和华法林组分别在另外 12 周内接受 MK-7 或华法林补充。对照组野生型小鼠接受普通饮食 24 周。所有小鼠均使用小动物正电子发射断层扫描(PET)/计算机断层扫描(CT)进行 Na[F]F 扫描。华法林组在 CT 上的主动脉近端出现点状钙化。所有斑点均与 von Kossa 染色的致密矿化相对应。在对照组之后,MK-7 组的 Na[F]F 摄取最低。晚期和华法林组在主动脉弓和左心室的摄取最高。晚期组没有出现点状钙化,但仍观察到 Na[F]F 摄取,提示存在微钙化。在新应用的小鼠模型中,CT 上仅在主动脉近端出现点状钙化,Na[F]F 似乎能有效监测斑块进展和维生素 K 对心血管疾病的有益作用。