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Protective Role of Clusterin/Apolipoprotein J Against Neointimal Hyperplasia via Antiproliferative Effect on Vascular Smooth Muscle Cells and Cytoprotective Effect on Endothelial Cells

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Author(s)
Han-Jong KimEun-Kyung Yoooon-Young KimYoung-Keun ChoiHyo-Jeong LeeJeong-Kook KimNam Ho JeoungKi-Up LeeIn-Sun ParkBon-Hong MinKeun-Gyu ParkChul-Ho LeeBruce J. AronowMasataka SataIn-Kyu Lee
Keimyung Author(s)
Park, Keun Gyu
Department
Dept. of Internal Medicine (내과학)
Journal Title
Arteriosclerosis, Thrombosis, and Vascular Biology
Issued Date
2009
Volume
29
Issue
10
Abstract
Objective—Clusterin is induced in vascular smooth muscle cells (VSMCs) during atherosclerosis and injury-induced neointimal
hyperplasia. However, its functional roles in VSMCs and endothelial cells remain controversial and elusive. This study was
undertaken to clarify the role of clusterin in neointimal hyperplasia and elucidate its mechanism of action.
Methods and Results—Adenovirus-mediated overexpression of clusterin (Ad-Clu) repressed TNF- –stimulated expression
of MCP-1, fractalkine, ICAM-1, VCAM-1, and MMP-9, leading to inhibition of VSMC migration. Both Ad-Clu
and secreted clusterin suppressed VSMC proliferation by inhibiting DNA synthesis, but not by inducing apoptosis.
Ad-Clu upregulated p53 and p21cip1/waf1 but downregulated cyclins D and E, leading to suppression of pRb
phosphorylation and subsequent induction of G1 arrest in VSMCs. Clusterin deficiency augmented VSMC proliferation
in vitro and accelerated neointimal hyperplasia in vivo, but concomitantly impaired reendothelialization in wire-injured
murine femoral arteries. Moreover, Ad-Clu significantly reduced neointimal thickening in balloon-injured rat carotid
arteries. Clusterin also diminished TNF- –induced apoptosis of human umbilical vein endothelial cells and restored
endothelial nitric oxide synthase expression suppressed by TNF- .
Conclusion—These results suggest that upregulation of clusterin during vascular injury may be a protective response against, rather
than a causative response to, the development of neointimal hyperplasia. (Arterioscler Thromb Vasc Biol. 2009;29:1558-1564.)
Key Words: clusterin VSMC endothelial cells proliferation neointimal hyperplasia
Keimyung Author(s)(Kor)
박근규
Publisher
School of Medicine
Citation
Han-Jong Kim et al. (2009). Protective Role of Clusterin/Apolipoprotein J Against Neointimal Hyperplasia via Antiproliferative Effect on Vascular Smooth Muscle Cells and Cytoprotective Effect on Endothelial Cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(10), 1558–1564. doi: 10.1161/ATVBAHA.109.190058
Type
Article
ISSN
1079-5642
DOI
10.1161/ATVBAHA.109.190058
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35101
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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