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Antioxidants
Volume 10
Issue 4
10.3390/antiox10040516
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Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis—Nitro-Redox Interconnections

by
Justine Bonetti
1,
Alessandro Corti
2,
Lucie Lerouge
1,
Alfonso Pompella
2,* and
Caroline Gaucher
1
1
CITHEFOR, Université de Lorraine, F-54000 Nancy, France
2
Department of Translational Research NTMS, University of Pisa Medical School, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
Academic Editors: Stefania Pizzimenti, Giuliana Muzio and Giuseppina Barrera
Antioxidants 2021, 10(4), 516; https://doi.org/10.3390/antiox10040516
Received: 1 March 2021 / Revised: 21 March 2021 / Accepted: 22 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Role of Oxidative Stress and Antioxidants in Pathophysiology: A Commemorative Special Issue in Honour of Professor Mario Umberto Dianzani)
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Abstract

Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cell types implicated in atherosclerosis development, and unlike other mature cell types, both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the vascular tone and the blood pressure. In response to vascular injury and modifications of the local environment (inflammation, oxidative stress), vSMCs switch from a contractile to a secretory phenotype and also display macrophagic markers expression and a macrophagic behaviour. Endothelial dysfunction promotes adhesion to the endothelium of monocytes, which infiltrate the sub-endothelium and differentiate into macrophages. The latter become polarised into M1 (pro-inflammatory), M2 (anti-inflammatory) or Mox macrophages (oxidative stress phenotype). Both monocyte-derived macrophages and macrophage-like vSMCs are able to internalise and accumulate oxLDL, leading to formation of “foam cells” within atherosclerotic plaques. Variations in the levels of nitric oxide (NO) can affect several of the molecular pathways implicated in the described phenomena. Elucidation of the underlying mechanisms could help to identify novel specific therapeutic targets, but to date much remains to be explored. The present article is an overview of the different factors and signalling pathways implicated in plaque formation and of the effects of NO on the molecular steps of the phenotypic switch of macrophages and vSMCs. View Full-Text
Keywords: atherosclerosis; macrophages; vascular smooth muscle cells; differentiation/de-differentiation; signalling pathways; nitric oxide atherosclerosis; macrophages; vascular smooth muscle cells; differentiation/de-differentiation; signalling pathways; nitric oxide
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MDPI and ACS Style

Bonetti, J.; Corti, A.; Lerouge, L.; Pompella, A.; Gaucher, C. Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis—Nitro-Redox Interconnections. Antioxidants 2021, 10, 516. https://doi.org/10.3390/antiox10040516

AMA Style

Bonetti J, Corti A, Lerouge L, Pompella A, Gaucher C. Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis—Nitro-Redox Interconnections. Antioxidants. 2021; 10(4):516. https://doi.org/10.3390/antiox10040516

Chicago/Turabian Style

Bonetti, Justine, Alessandro Corti, Lucie Lerouge, Alfonso Pompella, and Caroline Gaucher. 2021. "Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis—Nitro-Redox Interconnections" Antioxidants 10, no. 4: 516. https://doi.org/10.3390/antiox10040516

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