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(Circulation Research. 2006;99:918.)
© 2006 American Heart Association, Inc.

Editorials

Roads to Dysfunction

Argininase II Contributes to Oxidized Low-Density Lipoprotein-Induced Attenuation of Endothelial NO Production

Ralf P. Brandes

From the Institut für Kardiovaskuläre Physiologie, Goethe-Universität, Frankfurt am Main, Germany.

Correspondence to Ralf P. Brandes, MD, Institut für Kardiovaskuläre Physiologie, Fachbereich Medizin, J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany. E-mail r.brandes@em.uni-frankfurt.de

See related article, pages 951–960

Key Words: statins • arginase • hyperlipidemia • endothelial dysfunction • atherosclerosis • GTPases

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

Oxidized low-density lipoprotein (oxLDL) is considered to be the strongest proatherogenic lipoprotein. OxLDL is rapidly taken up by endothelial cells and macrophages and via the steps of foam cell formation and cell death, oxLDL eventually accumulates in the lipid core of atherosclerotic plaques.¹

The interaction of oxLDL with cells is mediated by several receptors.² Members of the scavenger receptor family predominate in macrophages,³ whereas endothelial cells mainly take up oxLDL by the lectin-like ox-LDL receptor-1 (LOX-1).⁴ On binding to LOX-1, oxLDL activates a multitude of signaling cascades involving MAP kinases,^5,6 protein kinase C (PKC),^7,8 and protein kinase B⁹ in endothelial cells. The consequence of this cellular activation, is apoptosis and superoxide anion production, the latter originating from the NADPH oxidase and uncoupling of the endothelial NO synthase (eNOS). OxLDL therefore is a strong inducer of endothelial dysfunction, a state in which the endothelium, instead of generating NO, produces superoxide anions. OxLDL also modulates the specific activity of NOS. It increases caveolin I expression and the interaction of NOS with this protein impairs NO production.¹⁰ Furthermore, oxLDL modulates PKC activity and expression and this family of kinases has been shown to acutely attenuate eNOS-dependent NO production and to promote eNOS uncoupling during prolonged exposure times.¹¹

Several observations suggest that the supply of eNOS with the substrate L-arginine is impaired in the presence of oxLDL: In hypercholesterolemia, supplementation of L-arginine improves endothelium-dependent relaxation and NO production;^12,13 L-arginine also attenuates the development of atherosclerosis,¹⁴ and normalizes leukocyte adhesion in hypercholesterolemia.¹⁵ . . . [Full Text of this Article]

Related Article:

Oxidized Low-Density Lipoprotein–Dependent Endothelial Arginase II Activation Contributes to Impaired Nitric Oxide Signaling

Sungwoo Ryoo, Christopher A. Lemmon, Kevin G. Soucy, Gaurav Gupta, Anthony R. White, Daniel Nyhan, Artin Shoukas, Lewis H. Romer, and Dan E. Berkowitz
Circ. Res. 2006 99: 951-960. [Abstract] [Full Text] [PDF]

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