Department of Neuroscience, Korea University College of Medicine, Seoul, Korea.
Department of Nuclear Medicine, Korea University Anam Hospital, Seoul, Korea.
Sci Rep. 2017 Aug 1;7(1):6989. doi: 10.1038/s41598-017-07073-3.
Synthetic vascular smooth muscle cells (VSMCs) play important roles in atherosclerosis, in-stent restenosis, and transplant vasculopathy. We investigated the synthetic activity of VSMCs in the atherosclerotic carotid artery using F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Atherosclerosis was induced in rats by partial ligation of the right carotid artery coupled with an atherogenic diet and vitamin D injections (2 consecutive days, 600,000 IU/day). One month later, rats were imaged by F-18 FDG PET. The atherosclerotic right carotid arteries showed prominent luminal narrowing with neointimal hyperplasia. The regions with neointimal hyperplasia were composed of α-smooth muscle actin-positive cells with decreased expression of smooth muscle myosin heavy chain. Surrogate markers of synthetic VSMCs such as collagen type III, cyclophilin A, and matrix metallopeptidase-9 were increased in neointima region. However, neither macrophages nor neutrophils were observed in regions with neointimal hyperplasia. F-18 FDG PET imaging and autoradiography showed elevated FDG uptake into the atherosclerotic carotid artery. The inner vessel layer showed higher tracer uptake than the outer layer. Consistently, the expression of glucose transporter 1 was highly increased in neointima. The present results indicate that F-18 FDG PET may be a useful tool for evaluating synthetic activities of VSMCs in vascular remodeling disorders.
合成血管平滑肌细胞(VSMCs)在动脉粥样硬化、支架内再狭窄和移植血管病中发挥重要作用。我们使用 F-氟脱氧葡萄糖(FDG)正电子发射断层扫描(PET)研究了动脉粥样硬化颈动脉中的 VSMC 的合成活性。通过右侧颈动脉部分结扎与致动脉粥样硬化饮食和维生素 D 注射(连续 2 天,每天 60 万 IU)诱导大鼠动脉粥样硬化。1 个月后,对大鼠进行 F-18 FDG PET 成像。动脉粥样硬化的右侧颈动脉显示明显的管腔狭窄伴新生内膜增生。新生内膜增生区域由α-平滑肌肌动蛋白阳性细胞组成,平滑肌肌球蛋白重链表达减少。在新生内膜区域,胶原 III 型、亲环素 A 和基质金属蛋白酶-9 等合成 VSMC 的替代标志物增加。然而,在新生内膜增生区域未观察到巨噬细胞或中性粒细胞。F-18 FDG PET 成像和放射自显影显示动脉粥样硬化颈动脉摄取 FDG 增加。血管内层的示踪剂摄取高于外层。一致地,葡萄糖转运蛋白 1 的表达在新生内膜中高度增加。本研究结果表明,F-18 FDG PET 可能是评估血管重构障碍中 VSMC 合成活性的有用工具。