Molecular mechanisms underlying the activation of eNOS

  • Ingrid Fleming
Cardiovascular Physiology


Endothelial cells situated at the interface between blood and the vessel wall play a crucial role in controlling vascular tone and homeostasis, particularly in determining the expression of pro- and anti-atherosclerotic genes. Many of these effects are mediated by changes in the generation and release of the vasodilator nitric oxide (NO) in response to hemodynamic stimuli exerted on the luminal surface of endothelial cells by the streaming blood (shear stress) and the cyclic strain of the vascular wall. The endothelial NO synthase (eNOS) is activated in response to fluid shear stress and numerous agonists via cellular events such as; increased intracellular Ca2+, interaction with substrate and co-factors, as well as adaptor and regulatory proteins, protein phosphorylation, and through shuttling between distinct sub-cellular domains. Dysregulation of these processes leads to attenuated eNOS activity and reduced NO output which is a characteristic feature of numerous patho-physiological disorders such as diabetes and atherosclerosis. This review summarizes some of the recent findings relating to the molecular events regulating eNOS activity.


Endothelium Mechanoreceptor Nitric oxide synthase Oxidative stress Phosphorylation Shear stress 



The author acknowledges the help of Dr. Beate Fisslthaler and Dr Annemarieke Loot in the preparation of the manuscript and the work of the many groups that was not possible to cite because of space limitations. The authors own work was supported by EICOSANOX, an integrated project supported by the European Community's sixth Framework Program (Contract N° LSHM-CT-2004-005033) and by the Deutsche Forschungsgemeinschaft (Exzellenzcluster 147 "Cardio-Pulmonary Systems").


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Institute for Vascular Signalling, Centre for Molecular MedicineJohann Wolfgang Goethe UniversityFrankfurt am MainGermany

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