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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1417.)
© 2006 American Heart Association, Inc.

Editorials

Beneficial Effects of Neuronal Nitric Oxide Synthase in Atherosclerosis

Charles J. Lowenstein

From the Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md.

Correspondence to Charles J. Lowenstein, 950 Ross Bldg, 720 Rutland Avenue, Baltimore, MD 21205. E-mail clowenst@jhmi.edu

Key Words: inflammation • endothelial • exocytosis • leukocyte • cholesterol • monocyte • macrophage

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

Endothelial nitric oxide synthase (eNOS) is the only NOS isoform expressed in normal coronary arteries. However, all 3 NOS isoforms—eNOS, inducible NOS (iNOS), and neuronal NOS (nNOS)—are found in human atherosclerotic plaques.¹ Precise studies of knockout mice have uncovered the role of eNOS and iNOS in atherogenesis (Figure). The eNOS isoform protects against atherosclerosis, because mice lacking eNOS have increased atherosclerotic plaques.^2,3 In contrast, iNOS is proatherogenic: iNOS knockout mice have decreased atherosclerotic plaque area.⁴ However, the role of nNOS in atherogenesis has remained a mystery until now.

View larger version (20K): [in this window] [in a new window]   All 3 isoforms of NOS are expressed in atherosclerotic plaques. Both nNOS and eNOS limit plaque size, whereas iNOS exacerbates atherosclerosis.

See page 1539

In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Kuhlencordt and colleagues explore the effects of deleting nNOS alleles on atherogenesis, by comparing the atherosclerotic burden in apoE^–/– mice and in nNOS^–/–/apoE^–/– mice fed a Western diet.⁵ The authors observed that nNOS decreases lesion area by 66% in male mice and by 31% in female mice. Unexpectedly, nNOS also improves survival: apoE^–/– mice also lacking nNOS had a 30% increase in mortality compared with apoE^–/– mice. Thus nNOS is doubly beneficial to mice predisposed to atherosclerosis: nNOS protects against atherosclerosis and decreases mortality. How?

Neuronal NOS might normally protect mice from atherosclerosis through indirect mechanisms. Expression of nNOS has been detected outside of the cardiovascular system in neurons, skeletal muscle, lung epithelia, and the kidney.^6–8 It is possible that nNOS regulates central nervous system . . . [Full Text of this Article]

Related Article:

Atheroprotective Effects of Neuronal Nitric Oxide Synthase in Apolipoprotein E Knockout Mice

Peter J. Kuhlencordt, Stefanie Hötten, Johannes Schödel, Sebastian Rützel, Kai Hu, Julian Widder, Alexander Marx, Paul L. Huang, and Georg Ertl
Arterioscler Thromb Vasc Biol 2006 26: 1539-1544. [Abstract] [Full Text] [PDF]

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