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Article

Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells

1
Division of Cardiology, Foundation for Medical Research, Department of Medicine Specialized Medicine, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, 1206 Geneva, Switzerland
2
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 6627, Brazil
3
Swiss Institute for Translational and Entrepreneurial Medicine, Freiburgstrasse 3, 3010 Bern, Switzerland
4
Ospedale Policlinico San Martino Genoa—Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Italy
5
First Clinic of Internal Medicine, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 6 Viale Benedetto XV, 16132 Genoa, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Raj Kishore
Cells 2022, 11(3), 411; https://doi.org/10.3390/cells11030411
Received: 24 December 2021 / Revised: 12 January 2022 / Accepted: 13 January 2022 / Published: 25 January 2022
Background: Atherosclerosis is a chronic inflammatory disease where macrophages participate in the progression of the disease. However, the role of resident-like macrophages (res-like) in the atherosclerotic aorta is not completely understood. Methods: A single-cell RNA sequencing analysis of CD45+ leukocytes in the atherosclerotic aorta of apolipoprotein E–deficient (Apoe−/−) mice on a normal cholesterol diet (NCD) or a high cholesterol diet (HCD), respecting the side-to-specific predisposition to atherosclerosis, was performed. A population of res-like macrophages expressing hyaluronan receptor LYVE-1 was investigated via flow cytometry, co-culture experiments, and immunofluorescence in human atherosclerotic plaques from carotid artery disease patients (CAD). Results: We identified 12 principal leukocyte clusters with distinct atherosclerosis disease-relevant gene expression signatures. LYVE-1+ res-like macrophages, expressing a high level of CC motif chemokine ligand 24 (CCL24, eotaxin-2), expanded under hypercholesteremia in Apoe−/− mice and promoted VSMC phenotypic modulation to osteoblast/chondrocyte-like cells, ex vivo, in a CCL24-dependent manner. Moreover, the abundance of LYVE-1+CCL24+ macrophages and elevated systemic levels of CCL24 were associated with vascular calcification and CAD events. Conclusions: LYVE-1 res-like macrophages, via the secretion of CCL24, promote the transdifferentiation of VSMC to osteogenic-like cells with a possible role in vascular calcification and likely a detrimental role in atherosclerotic plaque destabilization. View Full-Text
Keywords: resident-like macrophages; LYVE-1; CCL24; VSMC transdifferentiation; osteogenic-like cells; vascular calcification resident-like macrophages; LYVE-1; CCL24; VSMC transdifferentiation; osteogenic-like cells; vascular calcification
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MDPI and ACS Style

Burger, F.; Baptista, D.; Roth, A.; Brandt, K.J.; da Silva, R.F.; Montecucco, F.; Mach, F.; Miteva, K. Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells. Cells 2022, 11, 411. https://doi.org/10.3390/cells11030411

AMA Style

Burger F, Baptista D, Roth A, Brandt KJ, da Silva RF, Montecucco F, Mach F, Miteva K. Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells. Cells. 2022; 11(3):411. https://doi.org/10.3390/cells11030411

Chicago/Turabian Style

Burger, Fabienne, Daniela Baptista, Aline Roth, Karim J. Brandt, Rafaela F. da Silva, Fabrizio Montecucco, François Mach, and Kapka Miteva. 2022. "Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells" Cells 11, no. 3: 411. https://doi.org/10.3390/cells11030411

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