Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Modulation of Nitric Oxide Synthases by oxyLDL: Role in Vascular Inflammation and Atherosclerosis Development

Micaela Gliozzi
,
Miriam Scicchitano
,
Francesca Bosco
,
Vincenzo Musolino
,
Cristina Carresi
,
Federica Scarano
,
Jessica Maiuolo
,
Saverio Nucera
,
Alessia Maretta
,
Sara Paone
,
Rocco Mollace
,
Stefano Ruga
,
Maria Caterina Zito
,
Roberta Macrì
,
Francesca Oppedisano
,
Ernesto Palma
ORCID logo ,
Carolina Muscoli
,
Vincenzo Mollace
*
Version 1 : Received: 15 September 2018 / Approved: 17 September 2018 / Online: 17 September 2018 (07:45:14 CEST)

How to cite: Gliozzi, M.; Scicchitano, M.; Bosco, F.; Musolino, V.; Carresi, C.; Scarano, F.; Maiuolo, J.; Nucera, S.; Maretta, A.; Paone, S.; Mollace, R.; Ruga, S.; Zito, M.C.; Macrì, R.; Oppedisano, F.; Palma, E.; Muscoli, C.; Mollace, V. Modulation of Nitric Oxide Synthases by oxyLDL: Role in Vascular Inflammation and Atherosclerosis Development. Preprints 2018, 2018090285. https://doi.org/10.20944/preprints201809.0285.v1 Gliozzi, M.; Scicchitano, M.; Bosco, F.; Musolino, V.; Carresi, C.; Scarano, F.; Maiuolo, J.; Nucera, S.; Maretta, A.; Paone, S.; Mollace, R.; Ruga, S.; Zito, M.C.; Macrì, R.; Oppedisano, F.; Palma, E.; Muscoli, C.; Mollace, V. Modulation of Nitric Oxide Synthases by oxyLDL: Role in Vascular Inflammation and Atherosclerosis Development. Preprints 2018, 2018090285. https://doi.org/10.20944/preprints201809.0285.v1

Abstract

The release of nanomolar concentrations of nitric oxide (NO) by endothelial cells (EC), via activation of constitutive NO synthase (eNOS), represents the pre-requisite for the vaso-protective role of vascular endothelium. On the other hand, exaggerated release of NO as a consequence of activation of inducible NO synthase (iNOS), leads to endothelial dysfunction and, at the late stages, to the development of atherothrombosis. Oxidyzed LDLs (OxyLDL) represent the major candidate to trigger biomolecular processes accompanying endothelial dysfunction and vascular inflammation leading to atherosclerosis development though the pathophysiological mechanism still remains to be elucidated. Here, we summarize recent evidence suggesting that oxyLDL produce significant impairment in the balance in the eNOS/iNOS machinery, downregulating eNOS via HMGB1-TLR4-Caveolin-1 pathway. On the other hand, a sustained activation of the scavenger receptor LOX-1 leads to NFkB activation which, in turn, increases iNOS, leading to EC oxidative stress. Finally, these events are associated to reduced protective autophagic response and accelerated apoptotic EC death which activates atherosclerotic development. Taken togheter, these informations shed new light into the pathophysiological mechanisms of oxy-LDL-related impairment of EC functionality and open new perspective in atherothrombosis prevention.

Keywords

oxidized LDL; cNOS; iNOS; endothelial dysfunction

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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