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(Circulation Research. 2007;100:1534.)
© 2007 American Heart Association, Inc.

Editorials

LOX-1 and Atherosclerosis

Proof of Concept in LOX-1–Knockout Mice

Henning Morawietz

From the Department of Vascular Endothelium and Microcirculation, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Germany.

Correspondence to Henning Morawietz, PhD, Department of Vascular Endothelium and Microcirculation, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstr. 74, D-01307 Dresden, Germany. E-mail Henning.Morawietz@tu-dresden.de

See related article, pages 1634–1642

Key Words: atherosclerosis • LOX-1 • oxidized low-density lipoprotein • transgenic models

An extract of the first 250 words of the full text is provided, because this article has no abstract.

An increased plasma level of low-density lipoprotein (LDL) is a well-known risk factor for endothelial dysfunction and atherosclerosis.¹ The proatherosclerotic potential of LDL may even increase after oxidative modification to oxidized LDL (oxLDL),² whose uptake by macrophage scavenger receptors is thought to be a key process in the formation of foam cells, the hallmark of atherosclerotic lesions. However, there is less clarity on oxLDL uptake regulation in endothelial cells and its role in early stages of atherosclerosis.

A decade ago, Tatsuya Sawamura and colleagues discovered the lectin-like oxLDL receptor LOX-1 in endothelial cells.³ LOX-1 is a 50-kDa type II membrane glycoprotein and contains a short N-terminal cytoplasmic domain, a single transmembrane domain, a NECK domain or stalk, and an oxLDL-binding C-terminal extracellular C-type lectin-like domain. LOX-1 assembles on the cell surface in hexamer form or larger, comprising 3 homodimeric LOX-1 molecules bound to oxLDL.⁴

Although LOX-1 is expressed at very low levels in healthy endothelium, several lines of evidence support a role of LOX-1 in the pathogenesis of atherosclerosis.⁵ LOX-1 may be upregulated by its own ligand oxLDL or by proinflammatory cytokines in endothelial cells.⁶ Because proatherosclerotic angiotensin II^7,8 and endothelin-1⁹ vasoconstrictors increase endothelial LOX-1 expression and oxLDL uptake, LOX-1 has been suggested as a link between hypertension and atherogenesis.¹⁰ In line with these findings, a high-cholesterol diet induced intimal thickening and a marked increase in LOX-1 expression in the endothelium and neointima of rabbits, which was successfully reduced by an angiotensin II receptor type 1 antagonist.^11,12 Further support for . . . [Full Text of this Article]

Related Article:

Deletion of LOX-1 Reduces Atherogenesis in LDLR Knockout Mice Fed High Cholesterol Diet

Jawahar L. Mehta, Nobuhito Sanada, Chang Ping Hu, Jiawei Chen, Abhijit Dandapat, Fumiaki Sugawara, Hiroo Satoh, Kazuhiko Inoue, Yosuke Kawase, Kou-ichi Jishage, Hiroshi Suzuki, Motohiro Takeya, Laura Schnackenberg, Richard Beger, Paul L. Hermonat, Maria Thomas, and Tatsuya Sawamura
Circ. Res. 2007 100: 1634-1642. [Abstract] [Full Text] [PDF]

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