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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:959.)
© 2006 American Heart Association, Inc.

Editorials

Where Is Endothelial Nitric Oxide Synthase More Critical: Plasma Membrane or Golgi?

Zheng-Gen Jin

From the Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine, Rochester, NY.

Correspondence to Zheng-Gen Jin, Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine, 601 Elmwood Avenue, Box 679, Rochester, NY 14642. E-mail zheng-gen_jin@urmc.rochester.edu

Key Words: endothelial nitric oxide synthase • nitric oxide • endothelial cells • subcellular targeting • plasma membrane • Golgi • cholesterol

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

Vascular endothelium–derived nitric oxide (NO), originally identified as endothelium-derived relaxing factor,^1–3 plays a pivotal role in regulation of vascular homeostasis.⁴ NO is a major regulator of vascular tone and blood pressure, and has multiple antiatherogenic roles including antiinflammatory, antithrombotic, antiproliferative, and antioxidant effects.^4–6 Loss of the bioavailability of endothelium-derived NO is the hallmark of endothelial dysfunction and is implicated in the pathogenesis of cardiovascular disease such as hypertension and atherosclerosis.^7,8 Therefore, it is of great interest to understand the molecular mechanisms regulating NO production by endothelium, which is likely to provide new insight into endothelial function in health and disease.

See page 1015

Endothelial NO synthase (eNOS) is a highly regulated, calcium (Ca²⁺)/calmodulin (CaM)-dependent enzyme responsible for the physiological production of NO in the vasculature.^9,10 In endothelial cells (ECs), NO is formed from its precursor L-arginine via the enzymatic activation of eNOS with cofactors such as tetrahydrobiopterin (BH4). eNOS activation and subsequent NO production is stimulated by a variety of physical stimuli such as fluid shear stress generated by blood flow and by many humoral factors including acetylcholine, vascular endothelial growth factor (VEGF), bradykinin, estrogen, insulin, and angiopoietin.^10–12 Increasing evidence suggest that eNOS is regulated by subcellular localization,^9,13,14 posttranslational modifications such as phosphorylation at serine 1179 (S1179) by Akt,^15–17 and interactions with several regulatory proteins such as heat shock protein 90 (HSP90) and caveolin-1.^18,19 In particular, subcellular localization of eNOS is critical for optimal coupling of extracellular stimulation to NO production.¹⁰ In ECs, eNOS appears to localize at peripheral . . . [Full Text of this Article]

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Functional Relevance of Golgi- and Plasma Membrane-Localized Endothelial NO Synthase in Reconstituted Endothelial Cells

Qian Zhang, Jarrod E. Church, Davin Jagnandan, John D. Catravas, William C. Sessa, and David Fulton
Arterioscler Thromb Vasc Biol 2006 26: 1015-1021. [Abstract] [Full Text] [PDF]

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