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The eNOS signalosome and its link to endothelial dysfunction

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Abstract

Endothelial nitric oxide synthase (eNOS) plays an essential role in the regulation of endothelial function and acts as a master regulator of vascular tone and homeostasis through the generation of the gasotransmitter nitric oxide (NO). The complex network of events mediating efficient NO synthesis is regulated by post-translational modifications and protein-protein interactions. Dysregulation of these mechanisms induces endothelial dysfunction, a term often used to refer to reduced NO bioavailability and consequent alterations in endothelial function, that are a hallmark of many cardiovascular diseases. Endothelial dysfunction is linked to eNOS uncoupling, which consists of a switch from the generation of NO to the generation of superoxide anions and hydrogen peroxide. This review provides an overview of the eNOS signalosome, integrating past and recently described protein-protein interactions that have been shown to play a role in the modulation of eNOS activity with implications for cardiovascular pathophysiology. The mechanisms underlying eNOS uncoupling and clinically relevant strategies that were adopted to influence them are also discussed.

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Acknowledgments

We are grateful to Dr. Claudia Koch for her assistance in the preparation of the figures. This work was supported by the Deutsche Forschungsgemeinschaft (SFB 834/A9 and Exzellenzcluster 147 “Cardio-Pulmonary Systems”).

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  1. Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany

    Mauro Siragusa & Ingrid Fleming

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Siragusa, M., Fleming, I. The eNOS signalosome and its link to endothelial dysfunction. Pflugers Arch - Eur J Physiol 468, 1125–1137 (2016). https://doi.org/10.1007/s00424-016-1839-0

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