Preexisting smooth muscle cells contribute to neointimal cell repopulation at an incidence varying widely among individual lesions.
Preexisting smooth muscle cells contribute to neointimal cell repopulation at an incidence varying widely among individual lesions.
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DOI：
10.1016/j.surg.2015.08.015
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发表时间：
2016-02
期刊：
影响因子：
3.8
通讯作者：
Jiang Z
中科院分区：
文献类型：
--
作者：
Yang P;Hong MS;Fu C;Schmit BM;Su Y;Berceli SA;Jiang Z
由于新生内膜细胞来源的多样性，先前的研究已经证明了不同模型间新生内膜细胞谱系组成的差异，但动物与动物之间的差异并未引起太多的关注，尽管细胞的异质性可能影响新生内膜的生长及其对治疗干预的反应。利用R26R+；MYH11-Creer+和R26R+；scl-Creer+小鼠分别将LacZ标签附着在预先存在的平滑肌细胞(SMC)和内皮细胞(ECs)上。通过完全结扎颈总动脉(CCA)和对股动脉(FA)进行腔内损伤来造成新的内膜病变。在CCA和FA病变中，LacZ标记的SMCs从物理上从中层重新定位到新生内膜，并转变为去分化的表型。然而，新生内膜组织中SMC的含量在不同标本之间差异很大，分别为5-70%和0-85%，CCA(n=15)和FA(n=15)病变的平均含量分别为27%和29%。尽管骨髓细胞能够回到受损的动脉，但在任何一种类型的损伤后，骨髓细胞都不能完全分化为SMC。原存在的内皮细胞位于内皮下区，并产生间充质标记α-肌动蛋白，提示内皮细胞-间充质转化(EndoMT)，然而，EC来源的细胞仅占颈总动脉(n=7)和颈总动脉(n=7)新生内膜细胞池的7%和3%。位于管腔表面的ECS对EndoMT几乎没有证据。新生内膜增生的细胞成分在不同的病变之间有很大的差异。相对于内皮细胞，SMC是新血管内膜细胞谱系组成中病变间异质性的主要贡献者。
With the diverse origin of neointimal cells, previous studies have documented differences of neointimal cell-lineage composition across models, but the animal-to-animal difference has not attracted much attention though the cellular heterogeneity may impact neointimal growth and its response to therapeutic interventions. The R26R+;Myh11-CreER+ and R26R+;Scl-CreER+ mice were utilized to attach LacZ tags to the pre-existing smooth muscle cells (SMCs) and endothelial cells (ECs), respectively. Neointimal lesions were created via complete ligation of the common carotid artery (CCA) and transluminal injury to the femoral artery (FA). LacZ-tagged SMCs were physically relocated from media to neointima and changed to a de-differentiated phenotype in both CCA and FA lesions. The content of SMCs in the neointimal tissue, however, varied widely among specimens, ranging from 5–70% and 0–85%, with an average at low levels of 27% and 29% in CCA (n=15) and FA (n=15) lesions, respectively. Bone marrow cells, while able to home to the injured arteries, did not differentiate fully into SMCs after either type of injury. Pre-existing ECs were located in the sub-endothelial region and produced mesenchymal marker α-actin, indicating endothelial-mesenchymal-transition (EndoMT), however, EC-derived cells represented only 7% and 3% of the total neointimal cell pool of CCA (n=7) and FA (n=7) lesions, respectively. ECs located on the luminal surface exhibited little evidence for EndoMT. Neointimal hyperplasia proceeds with a wide range of variation in its cellular composition between individual lesions. Relative to ECs, SMCs are major contributors to the lesion-to-lesion heterogeneity in neointimal cell-lineage composition.