Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice
Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice
复制标题
DOI：
10.1161/01.atv.0000247243.48542.9d
复制
发表时间：
2006-12-01
影响因子：
8.7
通讯作者：
Falk, Erling
中科院分区：
文献类型：
--
作者：
Bentzon, Jacob F.;Weile, Charlotte;Falk, Erling
目的-最近对骨髓移植载脂蛋白E基因敲除(apoE(-/-))小鼠的研究表明，动脉粥样硬化中相当一部分的平滑肌细胞(SMC)来自于造血祖细胞。然而，这条途径仍然存在争议。在这项研究中，我们通过一系列的骨髓移植和在手术转移的动脉节段诱导的一种新的动脉粥样硬化模型中，重新检查了apoE(-/-)小鼠斑块的来源。方法和结果-我们分析了致死照射的apoE(-/-)小鼠的斑块，这些斑块是由来自EGFP(+)apoE(-/-)小鼠的性别不匹配的BM细胞重组的，这些小鼠普遍表达增强型绿色荧光蛋白(EGFP)，但在分析的大约10,000个SMC图谱中，没有发现一个来自供体BM来源的SMC。然后，我们将动脉节段移植到EGFP(+)apoE(-/-)和apoE(-/-)小鼠之间(除EGFP转基因外的同种移植)，并通过最近发明的套圈技术在移植物内局部诱导动脉粥样硬化。在移植到EGFP(+)apoE(-/-)小鼠体内的apoE(-/-)动脉节段形成的斑块中未发现EGFP(+)SMCs。将EGFP(+)apoE(-/-)小鼠动脉段移植到apoE(-/-)小鼠体内诱导的斑块中，96%的SMC为EGFP(+)。结论：apoE(-/-)小鼠动脉粥样硬化斑块中的SMC仅来源于局部血管壁。
Objective - Recent studies of bone marrow (BM)-transplanted apoE knockout ( apoE(-/-)) mice have concluded that a substantial fraction of smooth muscle cells (SMCs) in atherosclerosis arise from circulating progenitor cells of hematopoietic origin. This pathway, however, remains controversial. In the present study, we reexamined the origin of plaque SMCs in apoE(-/-) mice by a series of BM transplantations and in a novel model of atherosclerosis induced in surgically transferred arterial segments.Methods and Results - We analyzed plaques in lethally irradiated apoE(-/-) mice reconstituted with sex-mismatched BM cells from eGFP(+) apoE(-/-) mice, which ubiquitously express enhanced green fluorescent protein (eGFP), but did not find a single SMC of donor BM origin among approximate to 10 000 SMC profiles analyzed. We then transplanted arterial segments between eGFP(+) apoE(-/-) and apoE(-/-) mice (isotransplantation except for the eGFP transgene) and induced atherosclerosis focally within the graft by a recently invented collar technique. No eGFP(+) SMCs were found in plaques that developed in apoE(-/-) artery segments grafted into eGFP(+) apoE(-/-) mice. Concordantly, 96% of SMCs were eGFP(+) in plaques induced in eGFP(+) apoE(-/-) artery segments grafted into apoE(-/-) mice.Conclusions - These experiments show that SMCs in atherosclerotic plaques are exclusively derived from the local vessel wall in apoE(-/-) mice.