TY - JOUR
T1 - Effects of chemokine-like factor 1 on vascular smooth muscle cell migration and proliferation in vascular inflammation
AU - Zhang, Tao
AU - Zhang, Xiaoming
AU - Yu, Weidong
AU - Chen, Jian
AU - Li, Qingle
AU - Jiao, Yang
AU - He, Peiying
AU - Shen, Chenyang
N1 - Funding Information:
We thank Li Wang, Yaoyao Du and Bo Liu from the Peking University Health Science Center for technical assistance. We also thank Prof. Wenling Han and Ying Wang from the Laboratory of Medical Immunology, School of Basic Medical Science, Peking University, for the generous gifts of recombinant adenovirus carrying CKLF1, antibodies for CKLF1 and C19, S009. This work was supported by the National Natural Science Foundation of the People's Republic of China ( 30672039 ).
PY - 2013/1
Y1 - 2013/1
N2 - Objective: Vascular smooth muscle cell (VSMC) migration and proliferation are key components of vascular inflammation that may lead to atherosclerosis and restenosis, in which cytokines are considered as pivotal factors regarding recruitment of VSMC. A member of recently described family of chemokines, chemokine-like factor 1 (CKLF1), displays a wide spectrum of chemotaxis. This study investigated the role of CKLF1 in VSMC migration and proliferation during the process of vascular inflammation. Methods and results: : The effects of CKLF1 on migration, proliferation and neointimal formation were investigated in cultured VSMCs, rat balloon injured arteries and human atherosclerotic plaques. CKLF1 overexpression greatly enhanced, whereas shRNA knockdown markedly retarded, VSMC migration and proliferation in vitro. In addition, CKLF1 protein accumulated preferentially in neointima of the injured rat arteries in vivo. CKLF1 overexpression resulted in a 2.5-fold increase in intimal thickness. In contrast, shRNA-mediated CKLF1 knockdown significantly suppressed neointima formation by 70% compared that in control group. Intriguingly, besides animal model, higher level of CKLF1 was observed in human atherosclerotic plaques than that in normal arteries. Conclusion: CKLF1 plays an essential role in migration and proliferation of VSMCs, which in turn facilitated neointimal hyperplasia and atherosclerosis. Inhibition of CKLF1 activity provides a potential target for the prevention of atherosclerosis and restenosis.
AB - Objective: Vascular smooth muscle cell (VSMC) migration and proliferation are key components of vascular inflammation that may lead to atherosclerosis and restenosis, in which cytokines are considered as pivotal factors regarding recruitment of VSMC. A member of recently described family of chemokines, chemokine-like factor 1 (CKLF1), displays a wide spectrum of chemotaxis. This study investigated the role of CKLF1 in VSMC migration and proliferation during the process of vascular inflammation. Methods and results: : The effects of CKLF1 on migration, proliferation and neointimal formation were investigated in cultured VSMCs, rat balloon injured arteries and human atherosclerotic plaques. CKLF1 overexpression greatly enhanced, whereas shRNA knockdown markedly retarded, VSMC migration and proliferation in vitro. In addition, CKLF1 protein accumulated preferentially in neointima of the injured rat arteries in vivo. CKLF1 overexpression resulted in a 2.5-fold increase in intimal thickness. In contrast, shRNA-mediated CKLF1 knockdown significantly suppressed neointima formation by 70% compared that in control group. Intriguingly, besides animal model, higher level of CKLF1 was observed in human atherosclerotic plaques than that in normal arteries. Conclusion: CKLF1 plays an essential role in migration and proliferation of VSMCs, which in turn facilitated neointimal hyperplasia and atherosclerosis. Inhibition of CKLF1 activity provides a potential target for the prevention of atherosclerosis and restenosis.
KW - Atherosclerosis
KW - Chemokine-like factor 1
KW - Migration and proliferation
KW - Neointima formation
KW - Vascular smooth muscle cell
UR - http://www.scopus.com/inward/record.url?scp=84871387861&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2012.09.023
DO - 10.1016/j.atherosclerosis.2012.09.023
M3 - Article
C2 - 23102782
AN - SCOPUS:84871387861
SN - 0021-9150
VL - 226
SP - 49
EP - 57
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -