Endothelial nitric oxide synthase in the vascular wall: Mechanisms regulating its expression and enzymatic function

Michael Demosthenous; Charalambos Antoniades; Dimitris Tousoulis; Marios Margaritis; Kyriakoula Marinou; Christodoulos Stefanadis

doi:10.1016/j.artres.2011.03.003

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Volume 5, Issue 2, June 2011, Pages 37 - 49

Endothelial nitric oxide synthase in the vascular wall: Mechanisms regulating its expression and enzymatic function

Authors

Michael Demosthenous^a^{, c}, Charalambos Antoniades^a^{, c}^{, *}, Dimitris Tousoulis^a, Marios Margaritis^b, Kyriakoula Marinou^b, Christodoulos Stefanadis^a

^a1st Department of Cardiology, Athens University Medical School, Ileias 8, Gerakas Attikis, 153 44 Athens, Greece

^bDepartment of Experimental Physiology, Athens University Medical School, Athens, Greece

^c

Authors equally contributed.

^*Corresponding author. E-mail address: antoniades@vodafone.net.gr (C. Antoniades).

Corresponding Author

Charalambos Antoniades

Received 23 December 2009, Revised 26 February 2011, Accepted 24 March 2011, Available Online 21 April 2011.

DOI: 10.1016/j.artres.2011.03.003 How to use a DOI?
Keywords: eNOS; Nitric oxide; Tetrahydrobiopterin; Atherosclerosis
Abstract: Endothelial nitric oxide synthase (eNOS) is the main source of nitric oxide (NO) in the vascular wall, a molecule with anti-inflammatory, antithrombotic, vasorelaxant, antioxidant and finally antiatherogenic properties. eNOS is expressed in vascular endothelium, and it uses l-arginine as a substrate, while it also requires the presence of multiple co-factors such as tetrahydrobiopterin (BH4), nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) and others. In the presence of BH4 deficiency, this enzyme becomes uncoupled, and it is turned into a source of superoxide radicals instead of NO. Therefore, under these conditions which are present in patients with advanced atherosclerosis, eNOS in human vascular endothelium is largely a source of reactive oxygen species, inducing in this way atherogenesis. Therefore, the aim of future therapeutic strategies targeting atherosclerosis through regulation of eNOS physiology, should take into account that up-regulation of this enzyme in the vascular wall may not lead to a respective increase of NO bioavailability and improvement of vascular homeostasis, but it may actually induce intravascular oxidative stress, if intracellular bioavailability of eNOS co-factors is not simultaneously elevated. In conclusion, eNOS plays a critical role in the regulation of vascular homeostasis, and it is a therapeutic target against atherogenesis.
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Next Article In Issue>

Journal: Artery Research
Volume-Issue: 5 - 2
Pages: 37 - 49
Publication Date: 2011/04/21
ISSN (Online): 1876-4401
ISSN (Print): 1872-9312
DOI: 10.1016/j.artres.2011.03.003 How to use a DOI?
Open Access: This is an open access article distributed under the CC BY-NC license.

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ris enw bib

TY  - JOUR
AU  - Michael Demosthenous
AU  - Charalambos Antoniades
AU  - Dimitris Tousoulis
AU  - Marios Margaritis
AU  - Kyriakoula Marinou
AU  - Christodoulos Stefanadis
PY  - 2011
DA  - 2011/04/21
TI  - Endothelial nitric oxide synthase in the vascular wall: Mechanisms regulating its expression and enzymatic function
JO  - Artery Research
SP  - 37
EP  - 49
VL  - 5
IS  - 2
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2011.03.003
DO  - 10.1016/j.artres.2011.03.003
ID  - Demosthenous2011
ER  -

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