2007 Fiscal Year Final Research Report Summary
Novel functions of lectin-like oxidized LDL receptor-1 (LOX-1)
| Project/Area Number |
18590985
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kyoto University |
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Principal Investigator |
KUME Noriaki Kyoto University, Department of Cardiovascular Malicine, Associate Professor (20252455)
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| Project Period (FY) |
2006 – 2007
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| Keywords | atherosclerosis / remnant lipoproteins / LOX-1 / diabetes / metabolic syndrome / postprandial hyperlipidemia / vascular smooth muscle cells / HB-EGF |
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| Research Abstract |
Objective : Remnant-like lipoprotein particles (RLPs) have been implicated in atherogenesis especially by diabetic dyslipidemia ; however, their receptor(s) and effects on vascular smooth muscle cells (VSMCs) remain unclear. In this study, we examined if lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for RLPs and its biological effects in VSMCs. Methods : RLPs were isolated from human plasma by immunoaffinity gel containing anti-apolipoprotein A-I and anti-apolipoprotein B-100 monoclonal antibodies.
Results : DiI-labeled RLPs were taken up by CHO-K1 cells stably expressing LOX-1 but not by wild-type CHO-K1 cells. RLPs induced LOX-1 expression and cell migration in bovine VSMCs (BVSMCs), which were significantly suppressed by transfection with LOX-1 specific siRNAs. Inhibitors of metalloproteinases, epidermal growth factor (EGF) receptor tyrosine kinase, heparin-binding EGF-like growth factor (HB-EGF), p38 mitogen-activated protein kinase (p38 MAPK), MAPK kinase (MEK1), and phosphoinositide 3-kinase (PI3K) significantly blocked RLP-induced LOX-1 expression and cell migration of BVSMCs.
Conclusion : The present study provides direct evidence that LOX-1 is a novel receptor for RLPs in VSMCs. LOX-1-mediated uptake of RLPs may thus play important roles in atherogenesis by inducing LOX-1 expression and VSMC migration especially in the settings of postprandial hyperlipidemia, diabetes and metabolic syndrome.
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