Lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for remnant-like lipoprotein particles (RLPs) and mediates RLP-induced migration of vascular smooth muscle cells.
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.


RESULTS
RLPs were isolated from human plasma by immunoaffinity gel containing anti-apolipoprotein A-I and anti-apolipoprotein B-100 monoclonal antibodies. 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.


CONCLUSIONS
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.
Aramaki
Yo
Y
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Mitsuoka
Hirokazu
H
Toyohara
Masako
M
Jinnai
Toshikazu
T
Kanatani
Kazushi
K
Nakajima
Katsuyuki
K
Mukai
Eri
E
Yamada
Yuichiro
Y
Kita
Toru
T
Inagaki
Nobuya
N
Kume
Noriaki
N
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D002417:Cattle; D002465:Cell Movement; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D032342:Muscle Cells / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014280:Triglycerides / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008074:Lipoproteins; D051127:Scavenger Receptors, Class E; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases