title: Contribution of Vascular Cells to Neointimal Formation.
abstract: The de-differentiation and proliferation of smooth muscle cells (SMCs) are widely accepted as the major contributor to vascular remodeling. However, recent studies indicate that vascular stem cells (VSCs) also play an important role, but their relative contribution remains to be elucidated. In this study, we used genetic lineage tracing approach to further investigate the contribution of SMCs and VSCs to neointimal thickening in response to endothelium denudation injury or artery ligation. In vitro and in vivo analysis of MYH11-cre/Rosa-loxP-RFP mouse artery showed that SMCs proliferated at a much slower rate than non-SMCs. Upon denudation or ligation injury, two distinct types of neointima were identified: Type-I neointimal cells mainly involved SMCs, while Type II mainly involved non-SMCs. Using Sox10-cre/Rosa-loxP-LacZ mice, we found that Sox10+ cells were one of the cell sources in neointima. In addition, lineage tracing using Tie2-cre/Rosa-LoxP-RFP showed that endothelial cells also contributed to the neointimal formation, but rarely transdifferentiated into mesenchymal lineages. These results provide a novel insight into the contribution of vascular cells to neointima formation, and have significant impact on the development of more effective therapies that target specific vascular cell types.
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.|Department of Bioengineering, University of California, Berkeley, California, United States of America.
authors.forename: Falei
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California, United States of America.|Department of Bioengineering, University of California, Los Angeles, California, United States of America.|Department of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, Chong Qing University, Chongqing, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jixian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, Chong Qing University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California, United States of America.|Department of Bioengineering, University of California, Los Angeles, California, United States of America.|Department of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002339:Carotid Arteries / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D054338:Cell Transdifferentiation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D055757:SOXE Transcription Factors / Q000378:metabolism
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D015415:Biomarkers; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse