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Biomedicines
Volume 9
Issue 2
10.3390/biomedicines9020168
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Article

Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology

by
Susanna Fiorelli
1,
Nicola Cosentino
1,
Benedetta Porro
1,*,
Franco Fabbiocchi
1,
Giampaolo Niccoli
2,
Francesco Fracassi
2,
Nicolò Capra
1,
Simone Barbieri
1,
Filippo Crea
2,
Giancarlo Marenzi
1,
Viviana Cavalca
1,
Elena Tremoli
1 and
Sonia Eligini
1
1
Centro Cardiologico Monzino I.R.C.C.S., 20138 Milan, Italy
2
Dipartimento di Scienze Cardiovascolari e Toraciche, Fondazione Policlinico Gemelli I.R.C.C.S., Università Cattolica del Sacro Cuore, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2021, 9(2), 168; https://doi.org/10.3390/biomedicines9020168
Submission received: 28 December 2020 / Revised: 29 January 2021 / Accepted: 4 February 2021 / Published: 8 February 2021
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease)
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Abstract

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.
Keywords: monocyte-derived macrophages; Netrin-1; coronary artery plaque; atherosclerosis monocyte-derived macrophages; Netrin-1; coronary artery plaque; atherosclerosis

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MDPI and ACS Style

Fiorelli, S.; Cosentino, N.; Porro, B.; Fabbiocchi, F.; Niccoli, G.; Fracassi, F.; Capra, N.; Barbieri, S.; Crea, F.; Marenzi, G.; et al. Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology. Biomedicines 2021, 9, 168. https://doi.org/10.3390/biomedicines9020168

AMA Style

Fiorelli S, Cosentino N, Porro B, Fabbiocchi F, Niccoli G, Fracassi F, Capra N, Barbieri S, Crea F, Marenzi G, et al. Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology. Biomedicines. 2021; 9(2):168. https://doi.org/10.3390/biomedicines9020168

Chicago/Turabian Style

Fiorelli, Susanna, Nicola Cosentino, Benedetta Porro, Franco Fabbiocchi, Giampaolo Niccoli, Francesco Fracassi, Nicolò Capra, Simone Barbieri, Filippo Crea, Giancarlo Marenzi, and et al. 2021. "Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology" Biomedicines 9, no. 2: 168. https://doi.org/10.3390/biomedicines9020168

APA Style

Fiorelli, S., Cosentino, N., Porro, B., Fabbiocchi, F., Niccoli, G., Fracassi, F., Capra, N., Barbieri, S., Crea, F., Marenzi, G., Cavalca, V., Tremoli, E., & Eligini, S. (2021). Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology. Biomedicines, 9(2), 168. https://doi.org/10.3390/biomedicines9020168

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